Hepatocellular carcinoma (HCC) rupture and hemorrhage is one of the critical emergencies in HCC, with a high mortality rate upon occurrence. The mortality rate after rupture and hemorrhage is nearly 25%, while the recurrence rate of bleeding is approximately 20%, with a mortality rate exceeding 50%. Even after bleeding cessation, related complications pose significant challenges for treatment.
Case Presentation
Here, we report a case of multi-vessel rupture and hemorrhage in HCC, where initial hemostasis was successfully achieved via trans arterial embolization (TAE), but another vessel ruptured and bled again within 48 h. The total blood loss in this case was about 3300 mL, accompanied by severe complications such as infection, liver function deterioration, hepatic encephalopathy, and malnutrition. Additionally, we conducted a literature review on the mechanisms and treatment of HCC rupture and hemorrhage, aiming to provide insights and lessons for its diagnosis and management.
Conclusion
(1) After TAE for ruptured hepatocellular carcinoma with hemorrhage, it is still necessary to be vigilant against the possibility of secondary hemorrhage. During the TAE procedure, precise embolization should be achieved as much as possible to reduce liver function damage. (2) After ruptured hepatocellular carcinoma with hemorrhage, complications such as abdominal infection, hepatic encephalopathy, malnutrition, and deterioration of liver function need to be watched out for. Early identification and active intervention can help patients achieve better prognosis.
{"title":"A case report: Complications of trans arterial embolization in managing ruptured hemorrhage of hepatocellular carcinoma","authors":"Gang Tong, Yang Hua, Renhua Huang, Junwen Hu","doi":"10.1002/msp2.70025","DOIUrl":"https://doi.org/10.1002/msp2.70025","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) rupture and hemorrhage is one of the critical emergencies in HCC, with a high mortality rate upon occurrence. The mortality rate after rupture and hemorrhage is nearly 25%, while the recurrence rate of bleeding is approximately 20%, with a mortality rate exceeding 50%. Even after bleeding cessation, related complications pose significant challenges for treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Presentation</h3>\u0000 \u0000 <p>Here, we report a case of multi-vessel rupture and hemorrhage in HCC, where initial hemostasis was successfully achieved via trans arterial embolization (TAE), but another vessel ruptured and bled again within 48 h. The total blood loss in this case was about 3300 mL, accompanied by severe complications such as infection, liver function deterioration, hepatic encephalopathy, and malnutrition. Additionally, we conducted a literature review on the mechanisms and treatment of HCC rupture and hemorrhage, aiming to provide insights and lessons for its diagnosis and management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>(1) After TAE for ruptured hepatocellular carcinoma with hemorrhage, it is still necessary to be vigilant against the possibility of secondary hemorrhage. During the TAE procedure, precise embolization should be achieved as much as possible to reduce liver function damage. (2) After ruptured hepatocellular carcinoma with hemorrhage, complications such as abdominal infection, hepatic encephalopathy, malnutrition, and deterioration of liver function need to be watched out for. Early identification and active intervention can help patients achieve better prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100882,"journal":{"name":"Malignancy Spectrum","volume":"2 4","pages":"204-208"},"PeriodicalIF":0.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/msp2.70025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145842981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarcomatoid carcinoma is a rare and aggressive malignancy with a poor prognosis, capable of arising in diverse tissues. Pulmonary artery sarcomatoid carcinoma is particularly uncommon and highly invasive.
Case Presentation
We present the case of a 40-year-old male who experienced dry cough and dyspnea, and was subsequently diagnosed with a mass obstructing the bilateral main pulmonary artery, predominantly involving the left main branch shortly after contracting COVID-19. Histopathological analysis of a lung biopsy and positron emission tomography (PET) scan confirmed the diagnosis of sarcomatoid carcinoma involving the bilateral main pulmonary artery. Following six cycles of combined chemotherapy and immunotherapy, the patient's condition remained relatively stable.
Conclusion
This case report aims to discuss the clinical presentation, diagnostic approach, and therapeutic management of this rare condition, thereby contributing to the broader understanding of sarcomatoid carcinoma.
{"title":"Sarcomatoid carcinoma arising in the pulmonary artery","authors":"Huiting Zhang, Chunlei Li, Binglin Zhang, Hongzhu Long, Ting Yao, Zhenguo Zhai, Wanmu Xie","doi":"10.1002/msp2.70026","DOIUrl":"https://doi.org/10.1002/msp2.70026","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sarcomatoid carcinoma is a rare and aggressive malignancy with a poor prognosis, capable of arising in diverse tissues. Pulmonary artery sarcomatoid carcinoma is particularly uncommon and highly invasive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Presentation</h3>\u0000 \u0000 <p>We present the case of a 40-year-old male who experienced dry cough and dyspnea, and was subsequently diagnosed with a mass obstructing the bilateral main pulmonary artery, predominantly involving the left main branch shortly after contracting COVID-19. Histopathological analysis of a lung biopsy and positron emission tomography (PET) scan confirmed the diagnosis of sarcomatoid carcinoma involving the bilateral main pulmonary artery. Following six cycles of combined chemotherapy and immunotherapy, the patient's condition remained relatively stable.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This case report aims to discuss the clinical presentation, diagnostic approach, and therapeutic management of this rare condition, thereby contributing to the broader understanding of sarcomatoid carcinoma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100882,"journal":{"name":"Malignancy Spectrum","volume":"2 4","pages":"209-213"},"PeriodicalIF":0.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/msp2.70026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Saim Mahmood Khan, Jawairya Muhammad Hussain, Manahil Mubeen, Maryam Tariq, Zarnab Saleem, Marium Amjad, Laiba Bukhari, Iffa Habib, Hafiz Waqas Naseer, Mahnoor Khan, Hassan Saleem, Surraiya Riaz Mahmood Khan, Hudda Amjad, Aina Lashari
<p>Aromatase inhibitor-induced musculoskeletal symptoms (AIMSS), especially joint pain, have been widely reported in postmenopausal women undergoing endocrine therapy for hormone receptor-positive breast cancer and are a major cause of treatment termination. Aerobic exercise has emerged as a promising nonpharmacological intervention to counteract AIMSS in this population. This study aimed to perform a systematic review and meta-analysis to assess the effect of aerobic exercise on aromatase inhibitor-induced worst joint pain in postmenopausal breast cancer. A systematic literature search was performed using ClinicalTrials.gov, PubMed, and the Cochrane Library that yielded 1415 records. Studies comparing the effect of aerobic exercise with usual care on the worst joint pain through brief pain inventory (BPI) scoring in postmenopausal women with breast cancer receiving aromatase inhibitor therapy were included. For each group, the mean change from baseline and standard deviation (SD) of worst joint pain (BPI score) were calculated. Mean differences (MDs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Subgroup analyses were conducted to explore heterogeneity based on exercise intervention. Three randomized controlled trials (<i>n</i> = 297) were included. Pooled analysis showed no significant overall effect of exercise compared with control (standardized mean difference [SMD] = −0.16; 95% CI [−1.45, 1.14]; <i>p</i> = 0.65; <i>I</i><sup>2</sup> = 74%). Subgroup analysis indicated a significant difference by exercise type (<i>p</i> = 0.003), suggesting exercise modality influenced outcomes. Aerobic exercise, evaluated in two RCTs, significantly reduced worst joint pain (SMD = −0.41; 95% CI [−0.50, −0.32]; <i>p</i> = 0.01; <i>I</i><sup>2</sup> = 0%), indicating consistent benefit across studies. In contrast, the single study assessing Nordic walking showed no significant improvement (SMD = 0.56; 95% CI [−0.08, 1.19]; <i>p</i> = 0.08). Risk-of-bias assessment revealed variability across studies, with one trial rated low risk, one with some concerns, and one at high risk, which may partly explain the observed heterogeneity (<i>I</i><sup>2</sup> = 74%). Aerobic exercise interventions did not show an overall significant effect on the worst joint pain. However, subgroup analysis revealed that multi-component aerobic exercise programs were associated with significant pain reduction, while the study with only Nordic walking intervention was not. Considering the clinical burden of aromatase inhibitor-induced musculoskeletal symptoms, aerobic exercise can be a potentially useful non-pharmacologic adjunct to endocrine therapy. However, given the variation in the assessed risk of bias among the included studies, these outcomes should be interpreted with due caution. To confirm these results and determine the optimal exercise type and duration for managing aromatase inhibitor–associated musculoskeletal symptoms in breast cancer surviv
芳香酶抑制剂诱导的肌肉骨骼症状（AIMSS），特别是关节疼痛，在接受激素受体阳性乳腺癌内分泌治疗的绝经后妇女中已被广泛报道，并且是治疗终止的主要原因。有氧运动已成为一种有希望的非药物干预措施，以对抗这一人群的AIMSS。本研究旨在进行系统回顾和荟萃分析，以评估有氧运动对芳香酶抑制剂诱导的绝经后乳腺癌最严重关节疼痛的影响。使用ClinicalTrials.gov、PubMed和Cochrane图书馆进行了系统的文献检索，共获得1415条记录。在接受芳香酶抑制剂治疗的绝经后乳腺癌患者中，通过简短疼痛量表（BPI）评分，比较有氧运动与常规护理对最严重关节疼痛的影响。计算各组患者最严重关节痛（BPI评分）与基线的平均变化和标准差（SD）。使用随机效应模型合并95%置信区间（ci）的平均差异（MDs）。亚组分析探讨运动干预的异质性。纳入3项随机对照试验（n = 297）。综合分析显示，与对照组相比，运动没有显著的总体效果（标准化平均差[SMD] = - 0.16; 95% CI [- 1.45, 1.14]; p = 0.65; I2 = 74%）。亚组分析显示不同运动类型有显著差异（p = 0.003），表明运动方式影响结果。在两项随机对照试验中评估，有氧运动显著减少了最严重的关节疼痛（SMD = - 0.41; 95% CI [- 0.50, - 0.32]; p = 0.01; I2 = 0%），表明各研究的益处一致。相比之下，评估北欧步行的单一研究显示无显著改善（SMD = 0.56; 95% CI [- 0.08, 1.19]; p = 0.08）。偏倚风险评估揭示了研究之间的可变性，一个试验被评为低风险，一个有一些关注，一个高风险，这可能部分解释了观察到的异质性（I2 = 74%）。有氧运动干预对最严重的关节疼痛没有显示出总体上的显著影响。然而，亚组分析显示，多组分有氧运动计划与显著的疼痛减轻有关，而只有北欧步行干预的研究则没有。考虑到芳香酶抑制剂引起的肌肉骨骼症状的临床负担，有氧运动可能是内分泌治疗的一种潜在有用的非药物辅助疗法。然而，考虑到纳入研究中评估偏倚风险的差异，这些结果应谨慎解释。为了证实这些结果，并确定治疗乳腺癌幸存者芳香酶抑制剂相关肌肉骨骼症状的最佳运动类型和持续时间，需要进一步的大规模试验。
{"title":"Effect of aerobic exercise on worst joint pain in postmenopausal breast cancer women receiving aromatase inhibitors: A systematic review and meta-analysis","authors":"Saim Mahmood Khan, Jawairya Muhammad Hussain, Manahil Mubeen, Maryam Tariq, Zarnab Saleem, Marium Amjad, Laiba Bukhari, Iffa Habib, Hafiz Waqas Naseer, Mahnoor Khan, Hassan Saleem, Surraiya Riaz Mahmood Khan, Hudda Amjad, Aina Lashari","doi":"10.1002/msp2.70029","DOIUrl":"https://doi.org/10.1002/msp2.70029","url":null,"abstract":"<p>Aromatase inhibitor-induced musculoskeletal symptoms (AIMSS), especially joint pain, have been widely reported in postmenopausal women undergoing endocrine therapy for hormone receptor-positive breast cancer and are a major cause of treatment termination. Aerobic exercise has emerged as a promising nonpharmacological intervention to counteract AIMSS in this population. This study aimed to perform a systematic review and meta-analysis to assess the effect of aerobic exercise on aromatase inhibitor-induced worst joint pain in postmenopausal breast cancer. A systematic literature search was performed using ClinicalTrials.gov, PubMed, and the Cochrane Library that yielded 1415 records. Studies comparing the effect of aerobic exercise with usual care on the worst joint pain through brief pain inventory (BPI) scoring in postmenopausal women with breast cancer receiving aromatase inhibitor therapy were included. For each group, the mean change from baseline and standard deviation (SD) of worst joint pain (BPI score) were calculated. Mean differences (MDs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Subgroup analyses were conducted to explore heterogeneity based on exercise intervention. Three randomized controlled trials (<i>n</i> = 297) were included. Pooled analysis showed no significant overall effect of exercise compared with control (standardized mean difference [SMD] = −0.16; 95% CI [−1.45, 1.14]; <i>p</i> = 0.65; <i>I</i><sup>2</sup> = 74%). Subgroup analysis indicated a significant difference by exercise type (<i>p</i> = 0.003), suggesting exercise modality influenced outcomes. Aerobic exercise, evaluated in two RCTs, significantly reduced worst joint pain (SMD = −0.41; 95% CI [−0.50, −0.32]; <i>p</i> = 0.01; <i>I</i><sup>2</sup> = 0%), indicating consistent benefit across studies. In contrast, the single study assessing Nordic walking showed no significant improvement (SMD = 0.56; 95% CI [−0.08, 1.19]; <i>p</i> = 0.08). Risk-of-bias assessment revealed variability across studies, with one trial rated low risk, one with some concerns, and one at high risk, which may partly explain the observed heterogeneity (<i>I</i><sup>2</sup> = 74%). Aerobic exercise interventions did not show an overall significant effect on the worst joint pain. However, subgroup analysis revealed that multi-component aerobic exercise programs were associated with significant pain reduction, while the study with only Nordic walking intervention was not. Considering the clinical burden of aromatase inhibitor-induced musculoskeletal symptoms, aerobic exercise can be a potentially useful non-pharmacologic adjunct to endocrine therapy. However, given the variation in the assessed risk of bias among the included studies, these outcomes should be interpreted with due caution. To confirm these results and determine the optimal exercise type and duration for managing aromatase inhibitor–associated musculoskeletal symptoms in breast cancer surviv","PeriodicalId":100882,"journal":{"name":"Malignancy Spectrum","volume":"2 4","pages":"186-195"},"PeriodicalIF":0.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/msp2.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Harriet O'Rourke, Mahendra Naidoo, Oliver Piercey, Linda Mileshkin, Michael T. Fahey, Tamara Vu, Alexander G. Heriot, Jeanne Tie, Orla McNally, Anne Hamilton
Background
Malignant bowel obstruction (MBO) is a highly morbid complication of advanced intra-abdominal malignancies. This study aims to identify clinicopathologic factors and intervention strategies associated with improved survival and reduced rates of re-obstruction.
Methods
A single centre, retrospective data analysis was performed for all consecutive patients admitted with MBO to a tertiary cancer centre in Melbourne, Australia over a 2-year period.
Results
We identified a total of 102 patients with 137 admission episodes for MBO. Median age was 62 years, and 55 patients (54%) were female. 61 patients (60%) had a gastrointestinal primary (colorectal, gastric or appendiceal), while 17 patients (16%) had a gynaecological primary and 24 (24%) other primaries. Median overall survival was 120 days (95% confidence interval (CI) [76, 167]). 41 patients (40%) died within 90 days of initial admission with MBO. Clinicopathological variables associated with reduced 90-day survival included hypoalbuminaemia (odds ratio [OR] = 3.33 for serum albumin < 30 g/L, 95% CI [1.43, 7.69]) and peritoneal disease (OR = 5.80, 95% CI [2.26, 14.9]). 41 patients (40%) received surgical management. We identified no factors significantly associated with the decision for surgical rather than conservative management. Of the 113 total admissions that reached discharge, 55 (49%) were followed by patient readmission within 90 d. Almost half (48%) of patients were referred to the inpatient palliative care service and this was associated with a reduction in the odds of 90 d readmission (OR = 0.31, 95% CI [0.14, 0.71]).
Conclusion
MBO heralds a poor prognosis, with high rates of readmission, morbidity and mortality. Careful patient selection is imperative to identify patients likely to benefit from operative management.
{"title":"Bowel obstruction in advanced malignancies: An evaluation of patient outcomes at a tertiary cancer centre","authors":"Harriet O'Rourke, Mahendra Naidoo, Oliver Piercey, Linda Mileshkin, Michael T. Fahey, Tamara Vu, Alexander G. Heriot, Jeanne Tie, Orla McNally, Anne Hamilton","doi":"10.1002/msp2.70027","DOIUrl":"https://doi.org/10.1002/msp2.70027","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Malignant bowel obstruction (MBO) is a highly morbid complication of advanced intra-abdominal malignancies. This study aims to identify clinicopathologic factors and intervention strategies associated with improved survival and reduced rates of re-obstruction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A single centre, retrospective data analysis was performed for all consecutive patients admitted with MBO to a tertiary cancer centre in Melbourne, Australia over a 2-year period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified a total of 102 patients with 137 admission episodes for MBO. Median age was 62 years, and 55 patients (54%) were female. 61 patients (60%) had a gastrointestinal primary (colorectal, gastric or appendiceal), while 17 patients (16%) had a gynaecological primary and 24 (24%) other primaries. Median overall survival was 120 days (95% confidence interval (CI) [76, 167]). 41 patients (40%) died within 90 days of initial admission with MBO. Clinicopathological variables associated with reduced 90-day survival included hypoalbuminaemia (odds ratio [OR] = 3.33 for serum albumin < 30 g/L, 95% CI [1.43, 7.69]) and peritoneal disease (OR = 5.80, 95% CI [2.26, 14.9]). 41 patients (40%) received surgical management. We identified no factors significantly associated with the decision for surgical rather than conservative management. Of the 113 total admissions that reached discharge, 55 (49%) were followed by patient readmission within 90 d. Almost half (48%) of patients were referred to the inpatient palliative care service and this was associated with a reduction in the odds of 90 d readmission (OR = 0.31, 95% CI [0.14, 0.71]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>MBO heralds a poor prognosis, with high rates of readmission, morbidity and mortality. Careful patient selection is imperative to identify patients likely to benefit from operative management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100882,"journal":{"name":"Malignancy Spectrum","volume":"2 4","pages":"196-203"},"PeriodicalIF":0.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/msp2.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haider Imran, Zahra A. Haque, Minhal Imaan, Muhammad A. Aslam
<p>This Letter to the Editor is being written to respond to the article by Yao et al. (2025), which explores the role of non-apoptotic regulatory cell death (RCD) pathways in hepatocellular carcinoma (HCC) and their application in molecular prognostication.</p><p>HCC is one of the most common primary liver cancers, which accounts for 600,000 deaths annually, with a prognosis of 500,000–1,000,000 new annual cases [<span>1</span>]; hence, it remains a major global health challenge. Despite the advent of immune checkpoint inhibitors (ICIs), therapeutic responses remain suboptimal. Many patients exhibit intrinsic or acquired resistance due to immunosuppressive tumor microenvironment (TME), impaired antigen presentation, tumor heterogeneity, and microbiome-driven influences [<span>2</span>].</p><p>Nonapoptotic RCD, which includes ferroptosis, pyroptosis, and necroptosis, was presented by Yao et al. as a new axis affecting tumor immune behavior and resistance mechanisms [<span>3</span>]. Weighted gene co-expression network (WGCNA) and nonnegative matrix factorization (NMF) were applied to stratify HCC patients into three subtypes based on RCD gene expression, with ramifications for survival, immune infiltration, and drug responsiveness. A six-gene prognostic model was proposed to differentiate high- and low-risk patients, providing a more dynamic alternative to static biomarkers [<span>3, 4</span>].</p><p>This study highlighted a significant advancement in functional stratification and precision oncology for HCC. However, by integrating spatial transcriptomics, the potential can be further amplified as this will allow anatomical mapping of gene expression within the TME. Offering a spatial lens through which to interpret molecular profiles, with site-specific risks, RCD-driven suppressive niches, and spatially distinct immune-excluded areas as discovered by this approach [<span>5, 6</span>]. For example, immune-cold tumor regions that usually escape detection can be visualized, targeted, and analyzed using site-adapted therapies.</p><p>Moreover, the synergy of spatial omics with AI-enhanced digital pathology holds promise for real-time, image-guided biomarker prediction and dynamic patient monitoring [<span>7</span>]. Such an integration opens a next-generation frontier for tailoring immunotherapies and predicting treatment response with unprecedented granularity.</p><p>We applaud the authors' efforts to connect clinical knowledge with computational biology, and we encourage future research to validate their model prospectively across diverse, multiethnic cohorts. Incorporating RCD-based stratification within spatially aware, AI-integrated frameworks could redefine prognostication and therapy personalization in HCC, ushering in a new era of precision oncology.</p><p>Haider Imran contributed to writing the manuscript and reviewed the manuscript. Zahra Ali Haque contributed to editing the manuscript and came up with the concept. Minhal Imaan contributed
这封致编辑的信是为了回应Yao等人（2025）的文章，该文章探讨了非凋亡调节性细胞死亡（RCD）途径在肝细胞癌（HCC）中的作用及其在分子预后中的应用。HCC是最常见的原发性肝癌之一，每年有60万人死亡，预后为每年50万- 100万新发病例。因此，它仍然是一项重大的全球卫生挑战。尽管出现了免疫检查点抑制剂（ICIs），但治疗反应仍然不理想。由于免疫抑制肿瘤微环境（TME）、抗原呈递受损、肿瘤异质性和微生物组驱动的影响，许多患者表现出内在或获得性耐药。非凋亡性RCD，包括铁下垂（ferroptosis）、焦下垂（pyroptosis）和坏死性下垂（necroptosis），由Yao等人提出，是影响肿瘤免疫行为和耐药机制的新轴[b]。加权基因共表达网络（WGCNA）和非阴性基质因子分解（NMF）基于RCD基因表达将HCC患者分为三种亚型，并对生存、免疫浸润和药物反应性产生影响。提出了一个六基因预后模型来区分高风险和低风险患者，为静态生物标志物提供了一个更动态的选择[3,4]。这项研究强调了HCC的功能分层和精确肿瘤学的重大进展。然而，通过整合空间转录组学，可以进一步扩大潜力，因为这将允许在TME内进行基因表达的解剖定位。该方法提供了一个空间透镜，通过该透镜可以解释分子概况，包括位点特异性风险、rcd驱动的抑制性壁龛和空间上不同的免疫排斥区域[5,6]。例如，通常逃避检测的免疫冷肿瘤区域可以使用适应部位的治疗方法进行可视化、靶向和分析。此外，空间组学与人工智能增强的数字病理学的协同作用有望实现实时、图像引导的生物标志物预测和动态患者监测。这种整合为定制免疫疗法和以前所未有的粒度预测治疗反应开辟了下一代前沿。我们赞赏作者将临床知识与计算生物学联系起来的努力，我们鼓励未来的研究在不同的、多种族的人群中前瞻性地验证他们的模型。将基于rcd的分层纳入空间感知，人工智能集成框架可以重新定义HCC的预后和治疗个性化，迎来精准肿瘤学的新时代。海德尔·伊姆兰（Haider Imran）参与了手稿的撰写并审阅了手稿。扎赫拉·阿里·哈克（Zahra Ali Haque）参与了手稿的编辑，并提出了这个概念。Minhal Imaan为撰写手稿做出了贡献。穆罕默德·阿斯拉姆（Muhammad Aatir Aslam）为撰写手稿做出了贡献。作者声明无利益冲突。作者没有什么可报告的。
{"title":"From RCD pathways to precision oncology: A spatially-aware approach in HCC","authors":"Haider Imran, Zahra A. Haque, Minhal Imaan, Muhammad A. Aslam","doi":"10.1002/msp2.70028","DOIUrl":"https://doi.org/10.1002/msp2.70028","url":null,"abstract":"<p>This Letter to the Editor is being written to respond to the article by Yao et al. (2025), which explores the role of non-apoptotic regulatory cell death (RCD) pathways in hepatocellular carcinoma (HCC) and their application in molecular prognostication.</p><p>HCC is one of the most common primary liver cancers, which accounts for 600,000 deaths annually, with a prognosis of 500,000–1,000,000 new annual cases [<span>1</span>]; hence, it remains a major global health challenge. Despite the advent of immune checkpoint inhibitors (ICIs), therapeutic responses remain suboptimal. Many patients exhibit intrinsic or acquired resistance due to immunosuppressive tumor microenvironment (TME), impaired antigen presentation, tumor heterogeneity, and microbiome-driven influences [<span>2</span>].</p><p>Nonapoptotic RCD, which includes ferroptosis, pyroptosis, and necroptosis, was presented by Yao et al. as a new axis affecting tumor immune behavior and resistance mechanisms [<span>3</span>]. Weighted gene co-expression network (WGCNA) and nonnegative matrix factorization (NMF) were applied to stratify HCC patients into three subtypes based on RCD gene expression, with ramifications for survival, immune infiltration, and drug responsiveness. A six-gene prognostic model was proposed to differentiate high- and low-risk patients, providing a more dynamic alternative to static biomarkers [<span>3, 4</span>].</p><p>This study highlighted a significant advancement in functional stratification and precision oncology for HCC. However, by integrating spatial transcriptomics, the potential can be further amplified as this will allow anatomical mapping of gene expression within the TME. Offering a spatial lens through which to interpret molecular profiles, with site-specific risks, RCD-driven suppressive niches, and spatially distinct immune-excluded areas as discovered by this approach [<span>5, 6</span>]. For example, immune-cold tumor regions that usually escape detection can be visualized, targeted, and analyzed using site-adapted therapies.</p><p>Moreover, the synergy of spatial omics with AI-enhanced digital pathology holds promise for real-time, image-guided biomarker prediction and dynamic patient monitoring [<span>7</span>]. Such an integration opens a next-generation frontier for tailoring immunotherapies and predicting treatment response with unprecedented granularity.</p><p>We applaud the authors' efforts to connect clinical knowledge with computational biology, and we encourage future research to validate their model prospectively across diverse, multiethnic cohorts. Incorporating RCD-based stratification within spatially aware, AI-integrated frameworks could redefine prognostication and therapy personalization in HCC, ushering in a new era of precision oncology.</p><p>Haider Imran contributed to writing the manuscript and reviewed the manuscript. Zahra Ali Haque contributed to editing the manuscript and came up with the concept. Minhal Imaan contributed ","PeriodicalId":100882,"journal":{"name":"Malignancy Spectrum","volume":"2 4","pages":"214-215"},"PeriodicalIF":0.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/msp2.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Saim Mahmood Khan, Jawairya Muhammad Hussain, Manahil Mubeen, Aleeza Hasan, Haider Fizza, Muskan Shaikh, Maheen Khan, Surraiya Riaz Mahmood Khan, Syeda Faiqa Batool, Yuri André Ramírez Paliza, Syeda Saman Gul
Breast cancer (BC) is the most prevalent and destructive tumor in developing countries. The implementation of mammography screening programs has enabled access to appropriate therapeutic interventions, including adjuvant endocrine therapy and breast-conserving surgery; earlier diagnosis translates into a wider survival-rate range, making hypofractionated radiotherapy (HFRT) the preferred option. This review examines the current literature comparing the two radiation therapies, HFRT and conventional radiotherapy (CR), with reconstructed breasts, focusing on efficacy, toxicity, cosmetic outcomes, quality of life (QOL), and cost-effectiveness. A comprehensive literature search was conducted using major scientific databases, including PubMed, Scopus, Web of Science, and Google Scholar. The search focused on articles published primarily in English, from 2010 to 2024, and the period is about 15 years. The following search terms and Boolean operators were used: “hypofractionated radiotherapy” OR “hypofractionation” AND “breast cancer” AND “toxicity” OR “complications” OR “reconstruction” OR “quality of life” OR “HFRT versus CFRT” OR “intensity-modulated radiation therapy” OR “proton therapy”. CR can be safely replaced with HFRT in terms of overall survival and local recurrence rates. HFRT is associated with lesser risks of both acute and chronic side effects, breast complications, increased patient satisfaction, and reduced breast problems. In addition, new radiotherapy modalities, such as intensity-modulated radiation therapy, have shown great potential in targeting tumors. In treating BC, HFRT is gradually becoming standard, especially for patients who undergo reconstruction after surgery. Its low toxicity and equal effectiveness make it a key element in improving the QOL of BC survivors. It is recommended that future studies focus on long-term outcomes to provide better care to patients.
乳腺癌（BC）是发展中国家最普遍和最具破坏性的肿瘤。乳房x光检查项目的实施使人们能够获得适当的治疗干预措施，包括辅助内分泌治疗和保乳手术；早期诊断意味着更广泛的生存率范围，使低分割放疗（HFRT）成为首选。本文回顾了目前的文献，比较了两种放射治疗，HFRT和传统放疗（CR），重建乳房，重点是疗效，毒性，美容结果，生活质量（QOL）和成本效益。利用PubMed、Scopus、Web of Science、b谷歌Scholar等主要科学数据库进行了全面的文献检索。搜索主要集中在2010年至2024年期间以英语发表的文章，周期约为15年。使用以下搜索词和布尔运算符：“低分割放疗”或“低分割”与“乳腺癌”与“毒性”或“并发症”或“重建”或“生活质量”或“HFRT与CFRT”或“调强放射治疗”或“质子治疗”。就总生存率和局部复发率而言，HFRT可以安全地取代CR。HFRT与急性和慢性副作用、乳房并发症、提高患者满意度和减少乳房问题的风险较低有关。此外，新的放射治疗方式，如调强放射治疗，在靶向肿瘤方面显示出巨大的潜力。在治疗BC方面，HFRT正逐渐成为标准，特别是对于术后重建的患者。其低毒性和同等疗效使其成为改善BC幸存者生活质量的关键因素。建议未来的研究关注长期结果，为患者提供更好的护理。
{"title":"Hypofractionated versus conventionally fractionated radiotherapy for breast cancer in patients with reconstructed breast","authors":"Saim Mahmood Khan, Jawairya Muhammad Hussain, Manahil Mubeen, Aleeza Hasan, Haider Fizza, Muskan Shaikh, Maheen Khan, Surraiya Riaz Mahmood Khan, Syeda Faiqa Batool, Yuri André Ramírez Paliza, Syeda Saman Gul","doi":"10.1002/msp2.70024","DOIUrl":"https://doi.org/10.1002/msp2.70024","url":null,"abstract":"<p>Breast cancer (BC) is the most prevalent and destructive tumor in developing countries. The implementation of mammography screening programs has enabled access to appropriate therapeutic interventions, including adjuvant endocrine therapy and breast-conserving surgery; earlier diagnosis translates into a wider survival-rate range, making hypofractionated radiotherapy (HFRT) the preferred option. This review examines the current literature comparing the two radiation therapies, HFRT and conventional radiotherapy (CR), with reconstructed breasts, focusing on efficacy, toxicity, cosmetic outcomes, quality of life (QOL), and cost-effectiveness. A comprehensive literature search was conducted using major scientific databases, including PubMed, Scopus, Web of Science, and Google Scholar. The search focused on articles published primarily in English, from 2010 to 2024, and the period is about 15 years. The following search terms and Boolean operators were used: “hypofractionated radiotherapy” OR “hypofractionation” AND “breast cancer” AND “toxicity” OR “complications” OR “reconstruction” OR “quality of life” OR “HFRT versus CFRT” OR “intensity-modulated radiation therapy” OR “proton therapy”. CR can be safely replaced with HFRT in terms of overall survival and local recurrence rates. HFRT is associated with lesser risks of both acute and chronic side effects, breast complications, increased patient satisfaction, and reduced breast problems. In addition, new radiotherapy modalities, such as intensity-modulated radiation therapy, have shown great potential in targeting tumors. In treating BC, HFRT is gradually becoming standard, especially for patients who undergo reconstruction after surgery. Its low toxicity and equal effectiveness make it a key element in improving the QOL of BC survivors. It is recommended that future studies focus on long-term outcomes to provide better care to patients.</p>","PeriodicalId":100882,"journal":{"name":"Malignancy Spectrum","volume":"2 4","pages":"173-185"},"PeriodicalIF":0.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/msp2.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>Neurofibromatosis type 1 (NF-1) is an autosomal dominant, complex multi-system disorder that primarily affects the skin and nervous system. It is characterized by mutations in the <i>NF1</i> gene on chromosome 17, leading to abnormal production of neurofibromin protein. Common symptoms include café au lait spots, Lisch nodules, neurofibromas, plexiform neurofibromas, scoliosis, vision disorders, and learning and mental disabilities [<span>1</span>]. Managing NF-1 can be challenging because it is a lifelong disorder in which chronic pain is a prominent feature; consequently, opioids are prescribed and somnolence is frequently reported. Surgical interventions to remove tumors can also result in long-term physical impairments [<span>2</span>]. In recent years, new treatments like Selumetinib (Koselugo) have been approved. However, its effectiveness is mainly limited to children, and it can cause adverse effects like vomiting, raised creatinine phosphokinase, dry skin, and diarrhea [<span>3</span>]. A new development is the U.S. Food and Drug Administration's (FDA) approval on February 11, 2025 of mirdametinib (Gomekli), a mitogen-activated protein kinase kinase (MEK) inhibitor, for the treatment of adults and pediatric patients aged 2 years and older with NF-1-associated surgically inoperable plexiform neurofibromas. [<span>4</span>].</p><p>Loss of neurofibromin protein in NF-1 patients causes Ras signaling dysregulation. This results in MEK hyperactivation, driving uncontrolled cell growth and tumor formation. Mirdametinib, a specific noncompetitive MEK inhibitor (MEKi), blocks MEK activity, reducing hyperactivation of Ras and shrinkage of surgically inoperable plexiform neurofibromatosis. A Phase II trial assessed the safety and efficacy of mirdametinib in adolescents and adults of age ≥ 16 years with <i>NF1</i>-related plexiform neurofibromas. The results showed that mirdametinib is well-tolerated and effective, with a 42% partial response rate and at least 20% tumor shrinkage by volume [<span>5</span>].</p><p>The ReNeu trial, a pivotal Phase IIb study, evaluated the efficacy of mirdametinib in 114 patients. The results demonstrated a substantial confirmed objective response rate, durable reductions in plexiform neurofibromas volume, and clinically meaningful improvements in pain and health-related quality of life [<span>6</span>]. Crucially, mirdametinib stands out as a treatment distinct from traditional approaches like selumetinib, as it has been proved to be effective in the treatment for both children and adults.</p><p>Although mirdametinib represents a breakthrough for plexiform neurofibromas in NF-1, it carries a broad side-effect profile. Most commonly, cutaneous toxicities, including acneiform rash, eczema, seborrheic dermatitis, paronychia, and xerosis, have been reported [<span>7</span>], along with fatigue, profound changes in bile acid metabolism leading to nausea, vomiting, diarrhea [<span>8</span>], as well as MEKi-associated re
{"title":"Mirdametinib (Gomekli) wins FDA approval, bringing relief to NF-1 patients with surgically inoperable plexiform neurofibromatosis worldwide","authors":"Memuna J. Zeb","doi":"10.1002/msp2.70020","DOIUrl":"https://doi.org/10.1002/msp2.70020","url":null,"abstract":"<p>Neurofibromatosis type 1 (NF-1) is an autosomal dominant, complex multi-system disorder that primarily affects the skin and nervous system. It is characterized by mutations in the <i>NF1</i> gene on chromosome 17, leading to abnormal production of neurofibromin protein. Common symptoms include café au lait spots, Lisch nodules, neurofibromas, plexiform neurofibromas, scoliosis, vision disorders, and learning and mental disabilities [<span>1</span>]. Managing NF-1 can be challenging because it is a lifelong disorder in which chronic pain is a prominent feature; consequently, opioids are prescribed and somnolence is frequently reported. Surgical interventions to remove tumors can also result in long-term physical impairments [<span>2</span>]. In recent years, new treatments like Selumetinib (Koselugo) have been approved. However, its effectiveness is mainly limited to children, and it can cause adverse effects like vomiting, raised creatinine phosphokinase, dry skin, and diarrhea [<span>3</span>]. A new development is the U.S. Food and Drug Administration's (FDA) approval on February 11, 2025 of mirdametinib (Gomekli), a mitogen-activated protein kinase kinase (MEK) inhibitor, for the treatment of adults and pediatric patients aged 2 years and older with NF-1-associated surgically inoperable plexiform neurofibromas. [<span>4</span>].</p><p>Loss of neurofibromin protein in NF-1 patients causes Ras signaling dysregulation. This results in MEK hyperactivation, driving uncontrolled cell growth and tumor formation. Mirdametinib, a specific noncompetitive MEK inhibitor (MEKi), blocks MEK activity, reducing hyperactivation of Ras and shrinkage of surgically inoperable plexiform neurofibromatosis. A Phase II trial assessed the safety and efficacy of mirdametinib in adolescents and adults of age ≥ 16 years with <i>NF1</i>-related plexiform neurofibromas. The results showed that mirdametinib is well-tolerated and effective, with a 42% partial response rate and at least 20% tumor shrinkage by volume [<span>5</span>].</p><p>The ReNeu trial, a pivotal Phase IIb study, evaluated the efficacy of mirdametinib in 114 patients. The results demonstrated a substantial confirmed objective response rate, durable reductions in plexiform neurofibromas volume, and clinically meaningful improvements in pain and health-related quality of life [<span>6</span>]. Crucially, mirdametinib stands out as a treatment distinct from traditional approaches like selumetinib, as it has been proved to be effective in the treatment for both children and adults.</p><p>Although mirdametinib represents a breakthrough for plexiform neurofibromas in NF-1, it carries a broad side-effect profile. Most commonly, cutaneous toxicities, including acneiform rash, eczema, seborrheic dermatitis, paronychia, and xerosis, have been reported [<span>7</span>], along with fatigue, profound changes in bile acid metabolism leading to nausea, vomiting, diarrhea [<span>8</span>], as well as MEKi-associated re","PeriodicalId":100882,"journal":{"name":"Malignancy Spectrum","volume":"2 3","pages":"171-172"},"PeriodicalIF":0.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/msp2.70020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The combination of osimertinib and savolitinib as second-line treatment after epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance can significantly improve median progression-free survival (mPFS), objective response rate (ORR), and duration of remission (DOR). The combination therapy is safe and controllable, with no new safety signals or unexpected toxicity. However, the mechanism of drug resistance for tumor progression after dual-targeted therapy is currently unclear, and there is no clinical data reference for treatment after drug resistance. This case suggests some treatment options for lung adenocarcinoma patient after dual-targeted therapy with osimertinib and savolitinib.
Case presentation
A patient with EGFR-mutated lung adenocarcinoma developed mesenchymal–epithelial transition factor (MET) amplification-related resistance after first-line almonertinib. Subsequent sequential regimens—osimertinib plus savolitinib, chemo-immuno-antiangiogenesis therapy, and finally furmonertinib plus capmatinib—each yielded transient benefit.
Results
The report shows that the combination of chemotherapy and immunotherapy, as well as the dual-targeted therapy of firmonertinib and capmatinib, prolonged the overall survival of the patient.
Conclusions
This case suggests some treatment options for lung adenocarcinoma patient after dual-targeted therapy with osimertinib and savolitinib. The results indicated that traditional treatment or the combination of MET-TKI with another targeted therapy may improve the prognosis of patients.
{"title":"Chemotherapy + immunotherapy + anti-vascular therapy and firmonertinib + capmatinib prolong OS in EGFR-mutated and MET amplification following disease progression on osimertinib plus savolitinib: A case report of NSCLC","authors":"Ting Xu, Xiaohua Wang, Wanlin Shen, Mingxia Yang","doi":"10.1002/msp2.70018","DOIUrl":"https://doi.org/10.1002/msp2.70018","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Backgound</h3>\u0000 \u0000 <p>The combination of osimertinib and savolitinib as second-line treatment after epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance can significantly improve median progression-free survival (mPFS), objective response rate (ORR), and duration of remission (DOR). The combination therapy is safe and controllable, with no new safety signals or unexpected toxicity. However, the mechanism of drug resistance for tumor progression after dual-targeted therapy is currently unclear, and there is no clinical data reference for treatment after drug resistance. This case suggests some treatment options for lung adenocarcinoma patient after dual-targeted therapy with osimertinib and savolitinib.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case presentation</h3>\u0000 \u0000 <p>A patient with <i>EGFR</i>-mutated lung adenocarcinoma developed mesenchymal–epithelial transition factor (<i>MET</i>) amplification-related resistance after first-line almonertinib. Subsequent sequential regimens—osimertinib plus savolitinib, chemo-immuno-antiangiogenesis therapy, and finally furmonertinib plus capmatinib—each yielded transient benefit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The report shows that the combination of chemotherapy and immunotherapy, as well as the dual-targeted therapy of firmonertinib and capmatinib, prolonged the overall survival of the patient.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This case suggests some treatment options for lung adenocarcinoma patient after dual-targeted therapy with osimertinib and savolitinib. The results indicated that traditional treatment or the combination of MET-TKI with another targeted therapy may improve the prognosis of patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100882,"journal":{"name":"Malignancy Spectrum","volume":"2 3","pages":"151-158"},"PeriodicalIF":0.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/msp2.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hepatocellular carcinoma (HCC) is one of the deadliest cancer over the world. In this study, we aimed to determine the most critical molecular event in HCC patients with tumor protein p53 (TP53) or catenin beta 1 (CTNNB1) mutations, and to explore how these two mutations differ in their impact on HCC prognostication.
Methods
We performed an integrated comparative analysis of exome and transcriptome data from The Cancer Genome Atlas (TCGA) for HCC patients. Patient prognosis and correlation with the immune infiltration characteristics were performed. HCC cell line based in vitro experiments were also performed to validate the mechanistic insights.
Results
The 3-year progression-free survival (PFS) analysis of HCC patients with TP53 mutations indicated a significantly poorer clinical outcome compared to those with CTNNB1 mutations. Functional annotation of the TP53 mutant cohort revealed a substantial upregulation of genes associated with immune regulation, while the CTNNB1 mutant cohort displayed a prominent activation of metabolic pathways. Further comparative analysis and in vitro experiments showed that TP53 missense mutations activated the signal transducer and activator of transcription 3 (STAT3) signaling pathway, which fostered neutrophil infiltration and enhanced the enrichment of regulatory T (Treg) cells by secreting specific inflammatory molecules in the tumor microenvironment. Notably, treatment with a an STAT3 inhibitor suppressed the expression of these inflammatory molecules, underscoring how an immunosuppressive tumor microenvironment in the TP53 mutant cohort contributes to a poor prognosis.
Conclusion
Our study provides valuable insights, revealing that HCC patients with TP53 missense mutations exhibit a distinct immune profile associated with poorer clinical outcome compared to those with CTNNB1 mutations.
{"title":"Immune infiltration in TP53 missense mutant contributes to poor prognosis in hepatocellular carcinoma, unlike CTNNB1 mutations","authors":"Durgadevi Veeraiyan, Vishnu Kurpad, Vinayak Munirathnam, Chaitra V., Sonal Asthana, Akhileshwar Namani, Tapas Patra","doi":"10.1002/msp2.70015","DOIUrl":"https://doi.org/10.1002/msp2.70015","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) is one of the deadliest cancer over the world. In this study, we aimed to determine the most critical molecular event in HCC patients with tumor protein p53 (<i>TP53</i>) or catenin beta 1 (<i>CTNNB1</i>) mutations, and to explore how these two mutations differ in their impact on HCC prognostication.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed an integrated comparative analysis of exome and transcriptome data from The Cancer Genome Atlas (TCGA) for HCC patients. Patient prognosis and correlation with the immune infiltration characteristics were performed. HCC cell line based in vitro experiments were also performed to validate the mechanistic insights.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The 3-year progression-free survival (PFS) analysis of HCC patients with <i>TP53</i> mutations indicated a significantly poorer clinical outcome compared to those with <i>CTNNB1</i> mutations. Functional annotation of the <i>TP53</i> mutant cohort revealed a substantial upregulation of genes associated with immune regulation, while the <i>CTNNB1</i> mutant cohort displayed a prominent activation of metabolic pathways. Further comparative analysis and in vitro experiments showed that <i>TP53</i> missense mutations activated the signal transducer and activator of transcription 3 (STAT3) signaling pathway, which fostered neutrophil infiltration and enhanced the enrichment of regulatory T (Treg) cells by secreting specific inflammatory molecules in the tumor microenvironment. Notably, treatment with a an STAT3 inhibitor suppressed the expression of these inflammatory molecules, underscoring how an immunosuppressive tumor microenvironment in the <i>TP53</i> mutant cohort contributes to a poor prognosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study provides valuable insights, revealing that HCC patients with <i>TP53</i> missense mutations exhibit a distinct immune profile associated with poorer clinical outcome compared to those with <i>CTNNB1</i> mutations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100882,"journal":{"name":"Malignancy Spectrum","volume":"2 3","pages":"117-127"},"PeriodicalIF":0.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/msp2.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>Obesity is one of the burning lifestyle-related health problems of the current generation, affecting more than one-third of the global population. Obese individuals face a severe risk of various cancers, particularly concerning colorectal cancer (CRC), which has an extremely low survival rate among affected patients [<span>1</span>]. In fact, obesity is linked to 4%–8% of global cancer cases, and obese cancer patients face a 17% higher risk of mortality [<span>2</span>]. A recent report examined the relationship between obesity and four obesity-related cancers, namely cancers of the colon, rectum, pancreas, and kidney [<span>2</span>]. The study analyzed cancer incidence data from 42 countries and found positive correlation coefficients of 0.27 and 0.33 for colon cancer and rectal cancer, respectively [<span>2</span>]. Obesity-related CRC is associated with chronic low-grade inflammation, which may promote the progression of colorectal neoplasia through the inflammation–dysplasia–tumor sequence, particularly in early-onset cases. [<span>3</span>]. The risk of CRC in overweight/obese women under 50 years old has doubled, and a high-fat diet (HFD) consumed by a mother can lead to CRC in both mother and foetus [<span>4</span>]. Obesity modulates the CRC microenvironment, where the fat components are readily taken up by the tumor but not the CD8<sup>+</sup> T cells, thereby blocking tumor infiltration and blunting cancer immunotherapy [<span>5</span>]. In fact, HFD causes metabolic dysregulation by gut microbiota, increases the levels of lysophosphatidic acid, and promotes colorectal tumorigenesis [<span>6, 7</span>]. Similarly, the increase in the levels of palmitic acid in the blood caused by an HFD, which then leads to the activation of Toll-like receptor 4 (TLR4) in the colonic tissue, promotes growth, inflammatory pathogenesis, and CRC metastasis, and is directly associated with poor survival rates in patients with CRC [<span>8</span>]. Among the events, obesity-induced and/or obesity-associated pro-inflammatory milieu is majorly signaled by the adipokine, called fetuin-A or alpha-2-Heremans-Schmid glycoprotein (AHSG), whose serum level is positively correlated with visceral adipose tissue mass and body mass index (BMI, >30 kg/m<sup>2</sup>). Fetuin-A binds to TLR4 to induce inflammation-mediated fatty colon, interacts with membrane annexins (II and VI), and activates the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway to promote the proliferation of CRC cells. In contrast, adiponectin, a 30-kDa adipokine secreted by the adipocytes, prevents obesity through anti-inflammatory and hypolipidemic actions, and low adiponectin levels are associated with obesity, other inflammatory diseases, and poor prognosis across multiple cancer subtypes, including CRC [<span>8</span>]. Individuals with the highest serum levels of adiponectin possess around 60% less risk of CRC. Exogeneous adiponectin treatment was found to restric
{"title":"Fetuin-A:adiponectin ratio (FAR) as a critical biomarker in obesity-induced colorectal cancer?","authors":"Chandrani Fouzder, Subhadip Mukhopadhyay, Aditi Banerjee, Suprabhat Mukherjee","doi":"10.1002/msp2.70021","DOIUrl":"https://doi.org/10.1002/msp2.70021","url":null,"abstract":"<p>Obesity is one of the burning lifestyle-related health problems of the current generation, affecting more than one-third of the global population. Obese individuals face a severe risk of various cancers, particularly concerning colorectal cancer (CRC), which has an extremely low survival rate among affected patients [<span>1</span>]. In fact, obesity is linked to 4%–8% of global cancer cases, and obese cancer patients face a 17% higher risk of mortality [<span>2</span>]. A recent report examined the relationship between obesity and four obesity-related cancers, namely cancers of the colon, rectum, pancreas, and kidney [<span>2</span>]. The study analyzed cancer incidence data from 42 countries and found positive correlation coefficients of 0.27 and 0.33 for colon cancer and rectal cancer, respectively [<span>2</span>]. Obesity-related CRC is associated with chronic low-grade inflammation, which may promote the progression of colorectal neoplasia through the inflammation–dysplasia–tumor sequence, particularly in early-onset cases. [<span>3</span>]. The risk of CRC in overweight/obese women under 50 years old has doubled, and a high-fat diet (HFD) consumed by a mother can lead to CRC in both mother and foetus [<span>4</span>]. Obesity modulates the CRC microenvironment, where the fat components are readily taken up by the tumor but not the CD8<sup>+</sup> T cells, thereby blocking tumor infiltration and blunting cancer immunotherapy [<span>5</span>]. In fact, HFD causes metabolic dysregulation by gut microbiota, increases the levels of lysophosphatidic acid, and promotes colorectal tumorigenesis [<span>6, 7</span>]. Similarly, the increase in the levels of palmitic acid in the blood caused by an HFD, which then leads to the activation of Toll-like receptor 4 (TLR4) in the colonic tissue, promotes growth, inflammatory pathogenesis, and CRC metastasis, and is directly associated with poor survival rates in patients with CRC [<span>8</span>]. Among the events, obesity-induced and/or obesity-associated pro-inflammatory milieu is majorly signaled by the adipokine, called fetuin-A or alpha-2-Heremans-Schmid glycoprotein (AHSG), whose serum level is positively correlated with visceral adipose tissue mass and body mass index (BMI, >30 kg/m<sup>2</sup>). Fetuin-A binds to TLR4 to induce inflammation-mediated fatty colon, interacts with membrane annexins (II and VI), and activates the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway to promote the proliferation of CRC cells. In contrast, adiponectin, a 30-kDa adipokine secreted by the adipocytes, prevents obesity through anti-inflammatory and hypolipidemic actions, and low adiponectin levels are associated with obesity, other inflammatory diseases, and poor prognosis across multiple cancer subtypes, including CRC [<span>8</span>]. Individuals with the highest serum levels of adiponectin possess around 60% less risk of CRC. Exogeneous adiponectin treatment was found to restric","PeriodicalId":100882,"journal":{"name":"Malignancy Spectrum","volume":"2 3","pages":"167-170"},"PeriodicalIF":0.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/msp2.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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