Pub Date : 2024-09-12DOI: 10.1007/s00432-024-05933-w
Yuan Li, Aidong Gu, Lili Yang, Qingbo Wang
Background
Hepatocellular carcinoma (LIHC) has severe consequences due to late diagnosis and the lack of effective therapies. Currently, potential biomarkers for the diagnosis and prognosis of LIHC have not been systematically evaluated. Previous studies have reported that RAC1 is associated with the B cell receptor signaling pathway in various tumor microenvironments, but its relationship with LIHC remains unclear. We investigated the relationship between RAC1 and the prognosis and immune infiltration microenvironment of LIHC, exploring its potential as a prognostic biomarker for this type of cancer.
Methods
In this study, we analyzed data from The Cancer Genome Atlas (TCGA) using the Wilcoxon signed-rank test and logistic regression to assess the association between RAC1 expression and clinical characteristics in LIHC patients. Additionally, Kaplan-Meier and Cox regression methods were employed to confirm the impact of RAC1 expression levels on overall survival. Immunohistochemistry was used to validate RAC1 protein expression in LIHC. We constructed RAC1 knockdown LIHC cells and studied the effects of RAC1 protein on cell proliferation and migration at both cellular and animal levels.
Results
RAC1 expression levels were significantly elevated in LIHC tissues compared to normal tissues. High RAC1 expression was strongly associated with advanced pathological stages and was identified as an independent factor negatively affecting overall survival. At both cellular and animal levels, RAC1 knockdown significantly inhibited the proliferation and migration of LIHC cells. Furthermore, RAC1 expression was positively correlated with the infiltration of Th2 cells and macrophages in the tumor microenvironment, suggesting that RAC1 may contribute to the deterioration of the tumor immunosuppressive microenvironment and potentially lead to reduced patient survival.
Conclusion
These findings indicate that RAC1 expression promotes LIHC proliferation and migration and influences the landscape of immune cell infiltration in the tumor microenvironment. Based on these results, RAC1 is proposed as a potential prognostic biomarker for LIHC, associated with both cancer progression and tumor immune cell infiltration.
{"title":"RAC1 serves as a prognostic factor and correlated with immune infiltration in liver hepatocellular carcinoma","authors":"Yuan Li, Aidong Gu, Lili Yang, Qingbo Wang","doi":"10.1007/s00432-024-05933-w","DOIUrl":"https://doi.org/10.1007/s00432-024-05933-w","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Hepatocellular carcinoma (LIHC) has severe consequences due to late diagnosis and the lack of effective therapies. Currently, potential biomarkers for the diagnosis and prognosis of LIHC have not been systematically evaluated. Previous studies have reported that RAC1 is associated with the B cell receptor signaling pathway in various tumor microenvironments, but its relationship with LIHC remains unclear. We investigated the relationship between RAC1 and the prognosis and immune infiltration microenvironment of LIHC, exploring its potential as a prognostic biomarker for this type of cancer.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>In this study, we analyzed data from The Cancer Genome Atlas (TCGA) using the Wilcoxon signed-rank test and logistic regression to assess the association between RAC1 expression and clinical characteristics in LIHC patients. Additionally, Kaplan-Meier and Cox regression methods were employed to confirm the impact of RAC1 expression levels on overall survival. Immunohistochemistry was used to validate RAC1 protein expression in LIHC. We constructed RAC1 knockdown LIHC cells and studied the effects of RAC1 protein on cell proliferation and migration at both cellular and animal levels.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>RAC1 expression levels were significantly elevated in LIHC tissues compared to normal tissues. High RAC1 expression was strongly associated with advanced pathological stages and was identified as an independent factor negatively affecting overall survival. At both cellular and animal levels, RAC1 knockdown significantly inhibited the proliferation and migration of LIHC cells. Furthermore, RAC1 expression was positively correlated with the infiltration of Th2 cells and macrophages in the tumor microenvironment, suggesting that RAC1 may contribute to the deterioration of the tumor immunosuppressive microenvironment and potentially lead to reduced patient survival.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>These findings indicate that RAC1 expression promotes LIHC proliferation and migration and influences the landscape of immune cell infiltration in the tumor microenvironment. Based on these results, RAC1 is proposed as a potential prognostic biomarker for LIHC, associated with both cancer progression and tumor immune cell infiltration.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142198898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1007/s00432-024-05917-w
Dou-Dou Li, Teng Zhou, Jing Gao, Guan-Lin Wu, Guang-Rui Yang
Background and Objectives
Circadian rhythms, the endogenous biological clocks that govern physiological processes, have emerged as pivotal regulators in the development and progression of breast cancer. This comprehensive review delves into the intricate interplay between circadian disruption and breast tumorigenesis from multifaceted perspectives, encompassing biological rhythms, circadian gene regulation, tumor microenvironment dynamics, and genetic polymorphisms.
Methods and Results
Epidemiological evidence underscores the profound impact of external factors, such as night shift work, jet lag, dietary patterns, and exercise routines, on breast cancer risk and progression through the perturbation of circadian homeostasis. The review elucidates the distinct roles of key circadian genes, including CLOCK, BMAL1, PER, and CRY, in breast cancer biology, highlighting their therapeutic potential as molecular targets. Additionally, it investigates how circadian rhythm dysregulation shapes the tumor microenvironment, fostering epithelial-mesenchymal transition, chronic inflammation, and immunosuppression, thereby promoting tumor progression and metastasis. Furthermore, the review sheds light on the association between circadian gene polymorphisms and breast cancer susceptibility, paving the way for personalized risk assessment and tailored treatment strategies.
Conclusions
Importantly, it explores innovative therapeutic modalities that harness circadian rhythms, including chronotherapy, melatonin administration, and traditional Chinese medicine interventions. Overall, this comprehensive review emphasizes the critical role of circadian rhythms in the pathogenesis of breast cancer and highlights the promising prospects for the development of circadian rhythm-based interventions to enhance treatment efficacy and improve patient outcomes.
{"title":"Circadian rhythms and breast cancer: from molecular level to therapeutic advancements","authors":"Dou-Dou Li, Teng Zhou, Jing Gao, Guan-Lin Wu, Guang-Rui Yang","doi":"10.1007/s00432-024-05917-w","DOIUrl":"https://doi.org/10.1007/s00432-024-05917-w","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background and Objectives</h3><p>Circadian rhythms, the endogenous biological clocks that govern physiological processes, have emerged as pivotal regulators in the development and progression of breast cancer. This comprehensive review delves into the intricate interplay between circadian disruption and breast tumorigenesis from multifaceted perspectives, encompassing biological rhythms, circadian gene regulation, tumor microenvironment dynamics, and genetic polymorphisms.</p><h3 data-test=\"abstract-sub-heading\">Methods and Results</h3><p>Epidemiological evidence underscores the profound impact of external factors, such as night shift work, jet lag, dietary patterns, and exercise routines, on breast cancer risk and progression through the perturbation of circadian homeostasis. The review elucidates the distinct roles of key circadian genes, including CLOCK, BMAL1, PER, and CRY, in breast cancer biology, highlighting their therapeutic potential as molecular targets. Additionally, it investigates how circadian rhythm dysregulation shapes the tumor microenvironment, fostering epithelial-mesenchymal transition, chronic inflammation, and immunosuppression, thereby promoting tumor progression and metastasis. Furthermore, the review sheds light on the association between circadian gene polymorphisms and breast cancer susceptibility, paving the way for personalized risk assessment and tailored treatment strategies.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Importantly, it explores innovative therapeutic modalities that harness circadian rhythms, including chronotherapy, melatonin administration, and traditional Chinese medicine interventions. Overall, this comprehensive review emphasizes the critical role of circadian rhythms in the pathogenesis of breast cancer and highlights the promising prospects for the development of circadian rhythm-based interventions to enhance treatment efficacy and improve patient outcomes.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142225492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1007/s00432-024-05936-7
O. Ortmann, S. Schüler-Toprak, K. Kast
Purpose
To support doctors in counselling women with genetic predisposition for breast or gynecologic cancers on endocrine interventions.
Methods
Evidence on the safety of endocrine interventions for fertility treatment, contraception, hormone replacement therapy after risk-reducing salpingo-oophorectomy (RRSO) or treatment of symptoms during peri- and postmenopause was analysed for carriers of probably pathogenic and pathogenic variants in BRCA1 or BRCA2 (BRCA1/2-pV), in other breast and ovarian cancer genes and the Lynch Syndrome. Cancer risks were compared with data on risks for the general population.
Results
Data on risk modulation of endocrine interventions in women with genetic predisposition is limited. Ovarian hyperstimulation for fertility treatment may be performed. Oral contraceptives should not be used to reduce ovarian cancer risk in BRCA1/2-pV carriers. Premenopausal BRCA1/2-pV carriers and carriers of pV in Lynch Syndrome genes should be offered hormone replacement therapy (HRT) after RRSO, to prevent diseases caused by estrogen deficiency.
Conclusion
Effect direction and strength of risk modulation by endocrine interventions is similar to the general population. Participation of individuals at risk in prospective registries is recommended.
{"title":"The risk of endocrine interventions in carriers of a genetic predisposition for breast and gynecologic cancers: recommendations of the German Consortium for Hereditary Breast and Ovarian Cancer","authors":"O. Ortmann, S. Schüler-Toprak, K. Kast","doi":"10.1007/s00432-024-05936-7","DOIUrl":"https://doi.org/10.1007/s00432-024-05936-7","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>To support doctors in counselling women with genetic predisposition for breast or gynecologic cancers on endocrine interventions.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Evidence on the safety of endocrine interventions for fertility treatment, contraception, hormone replacement therapy after risk-reducing salpingo-oophorectomy (RRSO) or treatment of symptoms during peri- and postmenopause was analysed for carriers of probably pathogenic and pathogenic variants in <i>BRCA1</i> or <i>BRCA2</i> (<i>BRCA1/2</i>-pV), in other breast and ovarian cancer genes and the Lynch Syndrome. Cancer risks were compared with data on risks for the general population.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Data on risk modulation of endocrine interventions in women with genetic predisposition is limited. Ovarian hyperstimulation for fertility treatment may be performed. Oral contraceptives should not be used to reduce ovarian cancer risk in <i>BRCA1/2</i>-pV carriers. Premenopausal <i>BRCA1/2</i>-pV carriers and carriers of pV in Lynch Syndrome genes should be offered hormone replacement therapy (HRT) after RRSO, to prevent diseases caused by estrogen deficiency.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Effect direction and strength of risk modulation by endocrine interventions is similar to the general population. Participation of individuals at risk in prospective registries is recommended.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142225493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Gastric cancer (GC), a prevalent malignant tumor which is a leading cause of death from malignancy around the world. Peritoneal metastasis accounts for the major cause of mortality in patients with GC. Despite hyperthermia intraperitoneal chemotherapy (HIPEC) improves the therapeutic effect of GC, it's equivocal about the mechanism under HIPEC.
Methods: MiR-183-5p expression was sifted from miRNA chip and detected in both GC patients and cell lines by qRT-PCR. Gene interference and rescue experiments were performed to identified biological function in vitro and vivo. Next, we affirmed PPP2CA as targeted of miR-183-5p by dual luciferase reporter assay. Finally, the potential relationship between HIPEC and miR-183-5p was explored.
Results: MiR-183-5p is up-regulated in GC and associated with advanced stage and poor prognosis. MiR-183-5p accelerate GC migration in vitro which is influenced by miR-183-5p/PPP2CA/AKT/GSK3β/β-catenin Axis. HIPEC exerts migration inhibition via attenuating miR-183-5p expression.
Conclusion: MiR-183-5p can be used as a potential HIPEC biomarker in patients with CC.
{"title":"Paclitaxel hyperthermia suppresses gastric cancer migration through MiR-183-5p/PPP2CA/AKT/GSK3β/β-catenin axis.","authors":"Xiansheng Yang, Chang Liu, Zheng Li, Juncai Wen, Jinfu He, Yunxin Lu, Quanxing Liao, Tian Wang, Hongsheng Tang, Xianzi Yang, Lisi Zeng","doi":"10.1007/s00432-024-05923-y","DOIUrl":"https://doi.org/10.1007/s00432-024-05923-y","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC), a prevalent malignant tumor which is a leading cause of death from malignancy around the world. Peritoneal metastasis accounts for the major cause of mortality in patients with GC. Despite hyperthermia intraperitoneal chemotherapy (HIPEC) improves the therapeutic effect of GC, it's equivocal about the mechanism under HIPEC.</p><p><strong>Methods: </strong>MiR-183-5p expression was sifted from miRNA chip and detected in both GC patients and cell lines by qRT-PCR. Gene interference and rescue experiments were performed to identified biological function in vitro and vivo. Next, we affirmed PPP2CA as targeted of miR-183-5p by dual luciferase reporter assay. Finally, the potential relationship between HIPEC and miR-183-5p was explored.</p><p><strong>Results: </strong>MiR-183-5p is up-regulated in GC and associated with advanced stage and poor prognosis. MiR-183-5p accelerate GC migration in vitro which is influenced by miR-183-5p/PPP2CA/AKT/GSK3β/β-catenin Axis. HIPEC exerts migration inhibition via attenuating miR-183-5p expression.</p><p><strong>Conclusion: </strong>MiR-183-5p can be used as a potential HIPEC biomarker in patients with CC.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09DOI: 10.1007/s00432-024-05928-7
Axel Hegele, Rainer Häußermann, Stefan Schultheis, Lennart Skrobek, Meike Vink, Sebastian Hollwegs, Martin Ludwig, Petra Huwe, Manfred Maywurm, Anke Bartsch-Polle, Jost Weber, Markus Thiemer, Denny Varughese
Purpose: Apalutamide plus androgen-deprivation therapy (ADT) improved outcomes in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Nevertheless real-world data are limited. The aim of this multicenter study was to generate real-world data from nmCRPC patients treated with ADT plus apalutamide.
Methods: In this observational cohort based investigator initiated trial data of nmCRPC patients receiving apalutamide plus ADT were collected focusing on patient demographic data, prostate-specific antigen (PSA) declines, safety profile including dose modification/discontinuation as well as subsequent therapy and metastasis-free survival (MFS).
Results: Data from a total of 31 nmCRPC patients were documented. Compared to the Phase III study Spartan real-world patients are older, showed a higher ECOG-PS and more aggressive tumors. In the cohort PSA decreased about 98.1%, 74% of patients showed a PSA decrease over 90% and 54.8% reached a PSA-level < 0.2ng/ml. Apalutamide was well tolerated in real world patients: adverse events occurred in 67.7% but were in the majority mild (≥ grade 3: 6.5%). Dose reduction was necessary in 38.7% and 32.2% discontinued apalutamide treatment. MFS was 43 months and majority of patients were subsequently treated with abiraterone.
Conclusion: In real world more comorbid nmCRPC patients with a higher ECOG-PS and more aggressive tumors are treated with apalutamide plus ADT. Nevertheless efficacy results as well as side effects are similar in real-world compared to Spartan trial showing also a rapid, durable and deep PSA response with a median MFS of 43 months.
{"title":"Apalutamide for non-metastatic castration-resistant prostate cancer (nmCRPC): real world data of a multicenter study.","authors":"Axel Hegele, Rainer Häußermann, Stefan Schultheis, Lennart Skrobek, Meike Vink, Sebastian Hollwegs, Martin Ludwig, Petra Huwe, Manfred Maywurm, Anke Bartsch-Polle, Jost Weber, Markus Thiemer, Denny Varughese","doi":"10.1007/s00432-024-05928-7","DOIUrl":"https://doi.org/10.1007/s00432-024-05928-7","url":null,"abstract":"<p><strong>Purpose: </strong>Apalutamide plus androgen-deprivation therapy (ADT) improved outcomes in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Nevertheless real-world data are limited. The aim of this multicenter study was to generate real-world data from nmCRPC patients treated with ADT plus apalutamide.</p><p><strong>Methods: </strong>In this observational cohort based investigator initiated trial data of nmCRPC patients receiving apalutamide plus ADT were collected focusing on patient demographic data, prostate-specific antigen (PSA) declines, safety profile including dose modification/discontinuation as well as subsequent therapy and metastasis-free survival (MFS).</p><p><strong>Results: </strong>Data from a total of 31 nmCRPC patients were documented. Compared to the Phase III study Spartan real-world patients are older, showed a higher ECOG-PS and more aggressive tumors. In the cohort PSA decreased about 98.1%, 74% of patients showed a PSA decrease over 90% and 54.8% reached a PSA-level < 0.2ng/ml. Apalutamide was well tolerated in real world patients: adverse events occurred in 67.7% but were in the majority mild (≥ grade 3: 6.5%). Dose reduction was necessary in 38.7% and 32.2% discontinued apalutamide treatment. MFS was 43 months and majority of patients were subsequently treated with abiraterone.</p><p><strong>Conclusion: </strong>In real world more comorbid nmCRPC patients with a higher ECOG-PS and more aggressive tumors are treated with apalutamide plus ADT. Nevertheless efficacy results as well as side effects are similar in real-world compared to Spartan trial showing also a rapid, durable and deep PSA response with a median MFS of 43 months.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: To construct an integrative radiopathomics model for predicting progression-free survival (PFS) in nonmetastatic nasopharyngeal carcinoma (NPC) patients.
Methods: 357 NPC patients who underwent pretreatment MRI and pathological whole-slide imaging (WSI) were included in this study and randomly divided into two groups: a training set (n = 250) and validation set (n = 107). Radiomic features extracted from MRI were selected using the minimum redundancy maximum relevance and least absolute shrinkage and selection operator methods. The pathomics signature based on WSI was constructed using a deep learning architecture, the Swin Transformer. The radiopathomics model was constructed by incorporating three feature sets: the radiomics signature, pathomics signature, and independent clinical factors. The prognostic efficacy of the model was assessed using the concordance index (C-index). Kaplan-Meier curves for the stratified risk groups were tested by the log-rank test.
Results: The radiopathomics model exhibited superior predictive performance with C-indexes of 0.791 (95% confidence interval [CI]: 0.724-0.871) in the training set and 0.785 (95% CI: 0.716-0.875) in the validation set compared to any single-modality model (radiomics: 0.619, 95% CI: 0.553-0.706; pathomics: 0.732, 95% CI: 0.662-0.802; clinical model: 0.655, 95% CI: 0.581-0.728) (all, P < 0.05). The radiopathomics model effectively stratified patients into high- and low-risk groups in both the training and validation sets (P < 0.001).
Conclusion: The developed radiopathomics model demonstrated its reliability in predicting PFS for NPC patients. It effectively stratified individual patients into distinct risk groups, providing valuable insights for prognostic assessment.
目的:构建一个综合放射病理组学模型,用于预测非转移性鼻咽癌(NPC)患者的无进展生存期(PFS)。方法:本研究纳入了357例接受了治疗前核磁共振成像(MRI)和病理全切片成像(WSI)的鼻咽癌患者,并将其随机分为两组:训练集(n = 250)和验证集(n = 107)。从核磁共振成像中提取的放射组学特征采用最小冗余最大相关性、最小绝对收缩和选择算子法进行筛选。基于 WSI 的病理组学特征是使用深度学习架构 Swin Transformer 构建的。放射病理组学模型是通过整合三个特征集构建的:放射组学特征、病理组学特征和独立临床因素。该模型的预后效果使用一致性指数(C-index)进行评估。分层风险组的卡普兰-梅耶曲线通过对数秩检验进行检验:结果:放射病理组学模型显示出更优越的预测性能,与任何单一模式模型相比,训练集的C指数为0.791(95%置信区间[CI]:0.724-0.871),验证集的C指数为0.785(95% CI:0.716-0.875)(放射组学:0.619,95% CI:0.553-0.706;病理组学:0.732,95% CI:0.662-0.802;临床模型:0.655,95% CI:0.553-0.706):0.655,95% CI:0.581-0.728)(均为 P 结论:所开发的放射病理组学模型证明了其在预测鼻咽癌患者的生存期方面的可靠性。它有效地将患者分为不同的风险组别,为预后评估提供了有价值的见解。
{"title":"Integrative radiopathomics model for predicting progression-free survival in patients with nonmetastatic nasopharyngeal carcinoma.","authors":"Jing Hou, Xiaochun Yi, Handong Li, Qiang Lu, Huashan Lin, Junjun Li, Biao Zeng, Xiaoping Yu","doi":"10.1007/s00432-024-05930-z","DOIUrl":"https://doi.org/10.1007/s00432-024-05930-z","url":null,"abstract":"<p><strong>Purpose: </strong>To construct an integrative radiopathomics model for predicting progression-free survival (PFS) in nonmetastatic nasopharyngeal carcinoma (NPC) patients.</p><p><strong>Methods: </strong>357 NPC patients who underwent pretreatment MRI and pathological whole-slide imaging (WSI) were included in this study and randomly divided into two groups: a training set (n = 250) and validation set (n = 107). Radiomic features extracted from MRI were selected using the minimum redundancy maximum relevance and least absolute shrinkage and selection operator methods. The pathomics signature based on WSI was constructed using a deep learning architecture, the Swin Transformer. The radiopathomics model was constructed by incorporating three feature sets: the radiomics signature, pathomics signature, and independent clinical factors. The prognostic efficacy of the model was assessed using the concordance index (C-index). Kaplan-Meier curves for the stratified risk groups were tested by the log-rank test.</p><p><strong>Results: </strong>The radiopathomics model exhibited superior predictive performance with C-indexes of 0.791 (95% confidence interval [CI]: 0.724-0.871) in the training set and 0.785 (95% CI: 0.716-0.875) in the validation set compared to any single-modality model (radiomics: 0.619, 95% CI: 0.553-0.706; pathomics: 0.732, 95% CI: 0.662-0.802; clinical model: 0.655, 95% CI: 0.581-0.728) (all, P < 0.05). The radiopathomics model effectively stratified patients into high- and low-risk groups in both the training and validation sets (P < 0.001).</p><p><strong>Conclusion: </strong>The developed radiopathomics model demonstrated its reliability in predicting PFS for NPC patients. It effectively stratified individual patients into distinct risk groups, providing valuable insights for prognostic assessment.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-07DOI: 10.1007/s00432-024-05932-x
Guomin Gu, Chunling Liu, Xiaodan Zhu, Yan Yang, Shuming Song, Yan Zhao, Gang Sun
Purpose: Non-small cell lung cancer (NSCLC) is a highly fatal malignancy. The Kirsten rat sarcoma viral oncogene (KRAS) gene profoundly impacts patient prognosis. This study aims to explore the correlation between KRAS mutation subtypes, clinical data, and the impact of these subtypes on immunotherapy.
Materials and methods: Tumor samples from 269 NSCLC patients at the Affiliated Cancer Hospital of Xinjiang Medical University were analyzed. Patients received first- or second-line therapy without targeted therapy. Molecular and clinical data were used to analysis KRAS mutation subtypes and treatment outcomes.
Results: KRAS mutations predominantly included G12C, G12D, and G12V subtypes. TP53 had the highest mutation frequency among KRAS mutations, followed by MST1, STK11, and KMT2C. Gender differences were noted among KRAS mutation subtypes, with G12C and G12V mutations prevalent in males, while G12D mutations were less common among males. Smokers exhibited varied KRAS mutation subtypes, with G12C and G12V prevalent in smokers and G12D in nonsmokers. KRAS mutations were mainly in lung adenocarcinoma. TTF-1 and PD-L1 expression differed significantly among KRAS mutations. Patients with G12C and G12V mutations showed higher TMB levels and better immunotherapy outcomes compared to those without KRAS mutations. Conversely, patients with G12D mutations had poorer immunotherapy responses.
Conclusions: KRAS mutation subtypes exhibit distinct clinical and molecular characteristics and varying responses to immunotherapy. G12C and G12V mutations correlate with better immunotherapy outcomes, while G12D mutations are associated with poorer responses.
{"title":"Clinical characteristics of KRAS mutation subtypes in non-small cell lung cancer population in Xinjiang, China, and their impact on the prognosis of immunotherapy.","authors":"Guomin Gu, Chunling Liu, Xiaodan Zhu, Yan Yang, Shuming Song, Yan Zhao, Gang Sun","doi":"10.1007/s00432-024-05932-x","DOIUrl":"https://doi.org/10.1007/s00432-024-05932-x","url":null,"abstract":"<p><strong>Purpose: </strong>Non-small cell lung cancer (NSCLC) is a highly fatal malignancy. The Kirsten rat sarcoma viral oncogene (KRAS) gene profoundly impacts patient prognosis. This study aims to explore the correlation between KRAS mutation subtypes, clinical data, and the impact of these subtypes on immunotherapy.</p><p><strong>Materials and methods: </strong>Tumor samples from 269 NSCLC patients at the Affiliated Cancer Hospital of Xinjiang Medical University were analyzed. Patients received first- or second-line therapy without targeted therapy. Molecular and clinical data were used to analysis KRAS mutation subtypes and treatment outcomes.</p><p><strong>Results: </strong>KRAS mutations predominantly included G12C, G12D, and G12V subtypes. TP53 had the highest mutation frequency among KRAS mutations, followed by MST1, STK11, and KMT2C. Gender differences were noted among KRAS mutation subtypes, with G12C and G12V mutations prevalent in males, while G12D mutations were less common among males. Smokers exhibited varied KRAS mutation subtypes, with G12C and G12V prevalent in smokers and G12D in nonsmokers. KRAS mutations were mainly in lung adenocarcinoma. TTF-1 and PD-L1 expression differed significantly among KRAS mutations. Patients with G12C and G12V mutations showed higher TMB levels and better immunotherapy outcomes compared to those without KRAS mutations. Conversely, patients with G12D mutations had poorer immunotherapy responses.</p><p><strong>Conclusions: </strong>KRAS mutation subtypes exhibit distinct clinical and molecular characteristics and varying responses to immunotherapy. G12C and G12V mutations correlate with better immunotherapy outcomes, while G12D mutations are associated with poorer responses.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-06DOI: 10.1007/s00432-024-05914-z
Kangying Zhong, Yuqing Pei, Ziyan Yang, Qin Zheng
Purpose: Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by isolated thrombocytopenia that is often misdiagnosed due to the lack of a gold standard for diagnosis and currently relies on exclusionary approaches. This project combines several laboratory parameters to construct a clinical prediction model for adult ITP patients.
Methods: A total of 428 patients with thrombocytopenia who visited the West China Hospital of Sichuan University between January 2021 and March 2023 were enrolled. Based on the diagnostic criteria, we divided those patients into an ITP group and a non-ITP group. A total of 34 laboratory parameters were analyzed via univariate analysis and correlation analysis, and the least absolute shrinkage and selection operator regression analysis was used to establish the model. The training and validation sets were divided at a ratio of 7:3, and we used a fivefold cross-validation method to construct the model.
Results: The model included the following variables: red blood cell, mean corpuscular hemoglobin concentration, red blood cell distribution width-standard deviation, platelet variability index score, immature platelet fraction, lymphocyte absolute value. The prediction model exhibited good performance, with a sensitivity of 0.89 and a specificity of 0.83 in the training set and a sensitivity of 0.90 and a specificity of 0.87 in the validation set.
Conclusion: The clinical prediction model can assess the probability of ITP in thrombocytopenic patients and has good predictive accuracy for the diagnosis of ITP.
{"title":"Construction of a clinical prediction model for the diagnosis of immune thrombocytopenia based on clinical laboratory parameters.","authors":"Kangying Zhong, Yuqing Pei, Ziyan Yang, Qin Zheng","doi":"10.1007/s00432-024-05914-z","DOIUrl":"10.1007/s00432-024-05914-z","url":null,"abstract":"<p><strong>Purpose: </strong>Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by isolated thrombocytopenia that is often misdiagnosed due to the lack of a gold standard for diagnosis and currently relies on exclusionary approaches. This project combines several laboratory parameters to construct a clinical prediction model for adult ITP patients.</p><p><strong>Methods: </strong>A total of 428 patients with thrombocytopenia who visited the West China Hospital of Sichuan University between January 2021 and March 2023 were enrolled. Based on the diagnostic criteria, we divided those patients into an ITP group and a non-ITP group. A total of 34 laboratory parameters were analyzed via univariate analysis and correlation analysis, and the least absolute shrinkage and selection operator regression analysis was used to establish the model. The training and validation sets were divided at a ratio of 7:3, and we used a fivefold cross-validation method to construct the model.</p><p><strong>Results: </strong>The model included the following variables: red blood cell, mean corpuscular hemoglobin concentration, red blood cell distribution width-standard deviation, platelet variability index score, immature platelet fraction, lymphocyte absolute value. The prediction model exhibited good performance, with a sensitivity of 0.89 and a specificity of 0.83 in the training set and a sensitivity of 0.90 and a specificity of 0.87 in the validation set.</p><p><strong>Conclusion: </strong>The clinical prediction model can assess the probability of ITP in thrombocytopenic patients and has good predictive accuracy for the diagnosis of ITP.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-05DOI: 10.1007/s00432-024-05935-8
Ke Nie, Zhong-Jiang He, Ling-Jun Kong
Purpose: The aim of this study was to explore the potential correlation between the nuclear receptor subfamily 3 group C member 2 (NR3C2) and outcomes of colon cancer, along with the mechanisms underlying this association.
Method: mRNA (messenger RNA) data and clinical records pertaining to colon cancer were retrieved from The Cancer Genome Atlas (TCGA) database. The analysis of NR3C2 expression discrepancies between normal colon and tumor tissues was conducted using R software. In addition, we also studied the relationship between NR3C2 expression and prognosis, pathological parameters. The relative role of NR3C2 were further predicted through bioinformatics methods and receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of NR3C2 in colon cancer. Single-cell data from colon cancer samples in the GEO (Gene Expression Omnibus) database further investigated the mechanism of the lower survival associated with NR3C2 dysregulation. NR3C2 expression in three fresh colon cancer samples and their respective paracancer samples was determined. Furthermore, colon cancer cell models overexpressing NR3C2 and with knockdown NR3C2 were constructed by lentiviral vector transfection. Cell Counting Kit-8 assay, transplantation of tumors in nude mice and transwell assays were used to examine the proliferation, migration and invasion of colon cancer cells. The effect on the Wnt/β-catenin pathway, activities of cellular autophagy and cell apoptosis were examined by assessing the expression levels of several key proteins, including Bcl-2, Bax, and LC3.
Results: We found that NR3C2 was found a significantly lower level in colon cancer tissues than in adjacent tissues, which was associated with distant and lymphatic metastases, clinical stage, and poor clinical outcome, and it was an independent prognostic factor and potential marker of colon cancer. Single-cell transcriptome data identified the subset of circulating T and B cells with high expression of NR3C2, which is involved in TNF signaling pathway. Functional experiments show that downregulation of NR3C2 resultsed in the activation of the Wnt/β-catenin signaling pathway, and promotesd the proliferation and invasion of colon cancer cells while suppressing cell autophagy and apoptosis.
Conclusion: NR3C2 may regulate Wnt/β-catenin to affect the proliferation, invasion apoptosis and autophagy of colon cancer, and this axis is a potential target for the treatment of colon cancer.
{"title":"NR3C2 affects the proliferation and invasiveness of colon cancer cells through the Wnt/β-Catenin signaling pathway.","authors":"Ke Nie, Zhong-Jiang He, Ling-Jun Kong","doi":"10.1007/s00432-024-05935-8","DOIUrl":"10.1007/s00432-024-05935-8","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study was to explore the potential correlation between the nuclear receptor subfamily 3 group C member 2 (NR3C2) and outcomes of colon cancer, along with the mechanisms underlying this association.</p><p><strong>Method: </strong>mRNA (messenger RNA) data and clinical records pertaining to colon cancer were retrieved from The Cancer Genome Atlas (TCGA) database. The analysis of NR3C2 expression discrepancies between normal colon and tumor tissues was conducted using R software. In addition, we also studied the relationship between NR3C2 expression and prognosis, pathological parameters. The relative role of NR3C2 were further predicted through bioinformatics methods and receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of NR3C2 in colon cancer. Single-cell data from colon cancer samples in the GEO (Gene Expression Omnibus) database further investigated the mechanism of the lower survival associated with NR3C2 dysregulation. NR3C2 expression in three fresh colon cancer samples and their respective paracancer samples was determined. Furthermore, colon cancer cell models overexpressing NR3C2 and with knockdown NR3C2 were constructed by lentiviral vector transfection. Cell Counting Kit-8 assay, transplantation of tumors in nude mice and transwell assays were used to examine the proliferation, migration and invasion of colon cancer cells. The effect on the Wnt/β-catenin pathway, activities of cellular autophagy and cell apoptosis were examined by assessing the expression levels of several key proteins, including Bcl-2, Bax, and LC3.</p><p><strong>Results: </strong>We found that NR3C2 was found a significantly lower level in colon cancer tissues than in adjacent tissues, which was associated with distant and lymphatic metastases, clinical stage, and poor clinical outcome, and it was an independent prognostic factor and potential marker of colon cancer. Single-cell transcriptome data identified the subset of circulating T and B cells with high expression of NR3C2, which is involved in TNF signaling pathway. Functional experiments show that downregulation of NR3C2 resultsed in the activation of the Wnt/β-catenin signaling pathway, and promotesd the proliferation and invasion of colon cancer cells while suppressing cell autophagy and apoptosis.</p><p><strong>Conclusion: </strong>NR3C2 may regulate Wnt/β-catenin to affect the proliferation, invasion apoptosis and autophagy of colon cancer, and this axis is a potential target for the treatment of colon cancer.</p>","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-04DOI: 10.1007/s00432-024-05912-1
Aaron Lawson McLean
{"title":"Operationalizing urgency in oncology: ethical challenges amidst the pandemic.","authors":"Aaron Lawson McLean","doi":"10.1007/s00432-024-05912-1","DOIUrl":"10.1007/s00432-024-05912-1","url":null,"abstract":"","PeriodicalId":15118,"journal":{"name":"Journal of Cancer Research and Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}