Cancer Medicine最新文献_第9页

Frailty and Pre-Frailty in Patients With Lung Cancer and Its Association With Long-Term MACCE: A Longitudinal Cohort Study 肺癌患者的虚弱和虚弱前期及其与长期MACCE的关系：一项纵向队列研究。

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-12-08 DOI: 10.1002/cam4.71458

Fang Zhu, Qian Zhang, Hang Hao, Wenjie Cai, Qingquan Luo

Background

Lung cancer (LC) is a leading cause of morbidity and mortality worldwide. Cardiovascular disease is the primary cause of non-cancer-related death among cancer survivors. Frailty, characterized by a decline in physiological reserves, has been identified as a predictor of poor outcomes in cancer. However, the relationship between frailty, pre-frailty, and long-term cardiovascular outcomes in LC patients remains insufficiently explored.

Methods

This retrospective analysis of a cohort study utilized prospectively collected data from the UK Biobank, with baseline assessment between 2006 and 2010 and follow-up until October 31, 2022. Frailty was defined using the frailty phenotype according to five components (weight loss, exhaustion, low physical activity, slow gait speed, and low grip strength). Participants were categorized as non-frail, pre-frail or frail. The outcome was defined as major adverse cardiac and cerebrovascular events (MACCE). Cox proportional hazards models adjusted for confounders including age, sex, obesity, smoking status, socioeconomic status, diabetes, hypertension, COPD, and tumor type were employed to estimate hazard ratios (HR) for MACCE.

Results

Of the 500,530 participants in this cohort, 6095 were diagnosed with LC after recruitment. Among LC patients, 43.79% were non-frail, 48.20% pre-frail, and 8.01% frail. Frail individuals had a significantly higher risk of MACCE (HR = 1.21, 95% CI: 1.07–1.38, p = 0.002) compared to non-frail patients, while pre-frail individuals also exhibited an elevated risk (HR = 1.10, 95% CI: 1.02–1.18, p = 0.010). Specific frailty components, particularly low physical activity and slow gait speed, were strongly associated with increased risks of both MACCE and all-cause mortality. In contrast, low grip strength did not show a significant association with adverse outcomes.

Conclusions

LC participants had a higher prevalence of pre-frailty and frailty. The presence of frailty and pre-frailty significantly increased the risk of MACCE in long-term LC survivors. Notably, slow gait speed and low physical activity were strongly associated with MACCE compared to other frailty components.

背景：肺癌（LC）是全球发病率和死亡率的主要原因。心血管疾病是癌症幸存者中非癌症相关死亡的主要原因。身体虚弱，以生理储备下降为特征，已被确定为癌症预后不良的预测指标。然而，LC患者虚弱、虚弱前期和长期心血管预后之间的关系仍未得到充分探讨。方法：回顾性分析一项队列研究，利用从英国生物银行前瞻性收集的数据，在2006年至2010年期间进行基线评估，并随访至2022年10月31日。虚弱是根据五个组成部分（体重减轻、疲惫、低体力活动、慢速步态和低握力）定义的虚弱表型。参与者被分为非体弱、体弱前和体弱。结果定义为主要心脑血管不良事件（MACCE）。采用Cox比例风险模型校正混杂因素，包括年龄、性别、肥胖、吸烟状况、社会经济状况、糖尿病、高血压、COPD和肿瘤类型，以估计MACCE的风险比（HR）。结果：在该队列的500,530名参与者中，6095名在招募后被诊断为LC。在LC患者中，43.79%为非虚弱，48.20%为虚弱前期，8.01%为虚弱。与非体弱患者相比，体弱个体发生MACCE的风险明显更高（HR = 1.21, 95% CI: 1.07-1.38, p = 0.002），而体弱前个体也表现出较高的风险（HR = 1.10, 95% CI: 1.02-1.18, p = 0.010）。特定的虚弱因素，特别是低体力活动和缓慢的步态速度，与MACCE和全因死亡率的风险增加密切相关。相反，低握力与不良结果没有显著的关联。结论：LC参与者有较高的前期虚弱和虚弱患病率。衰弱和衰弱前期的存在显著增加了长期LC幸存者发生MACCE的风险。值得注意的是，与其他虚弱因素相比，缓慢的步态速度和低体力活动与MACCE密切相关。

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引用次数: 0

Tumor Genomic and Transcriptomic Analysis Integrated With Liquid Biopsy ctDNA Monitoring: Analytical Validation and Clinical Insights 肿瘤基因组学和转录组学分析结合液体活检ctDNA监测：分析验证和临床见解。

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-12-08 DOI: 10.1002/cam4.71465

Nam H. B. Tran, Thien-Phuc Hoang Nguyen, Vinh Quang Bui, Vu Thuong Le, Trong Khoa Mai, Van-Anh Nguyen Hoang, Tien Anh Nguyen, Minh-Duc Nguyen, Ha-Hieu Pham, Tho Thi Le Vo, My T. T. Ngo, Du Quyen Nguyen, Duy Sinh Nguyen, Hoai-Nghia Nguyen, Minh-Duy Phan, Hoa Giang, Lan N. Tu

Background

Comprehensive genomic profiling (CGP) is a time- and tissue- efficient method to help guide precision oncology. To enhance the clinical utility of CGP, we investigated the performance of a novel strategy integrating tumor DNA and mRNA profiling, together with liquid biopsy ctDNA monitoring.

Methods

Genomic DNA and mRNA simultaneously extracted from 604 archived tissue samples of 12 cancer types were used. Tumor DNA was subjected to targeted sequencing using a 504-gene panel with high-density probes (HDP), and shallow whole genome sequencing to profile genomic biomarkers. mRNA transcriptome profiling was performed to further capture fusion variants, and to predict tissue of origin (TOO) using our ensemble model OriCUP, an algorithm trained on 9889 samples and independently validated on 731 samples. In a cohort of 55 metastatic lung cancer patients, longitudinal plasma ctDNA was analyzed using a hybrid tumor-informed and tumor-agnostic approach to predict progression-free survival (PFS).

Results

Among all biomarkers, DNA sequencing using HDP achieved higher sensitivity than the standard panel design to identify copy number variations at chromosome-, gene-, and exon- levels. The detection rate of fusion variants using DNA sequencing alone was 20% lower than mRNA sequencing in reference samples, while the combination of both methods was essential to maximize fusion detection in clinical FFPE samples. For TOO, our OriCup model achieved prediction accuracy of 87.7% for primary tumors and 81.4% for metastatic tumors. In 55 lung cancer patients, ctDNA profiling identified additional 11.5% tumor-agnostic actionable and resistance mutations. Patients having more than 50% ctDNA decrease from baseline were classified as molecular responders and showed significantly longer PFS than those classified as molecular non-responders (HR = 9.42, 95% CI: 3.33–26.67, p < 0.0001, 12-month PFS: 95.5% vs. 31.7%).

Conclusions

Comprehensive genomic and transcriptomic profiling could reliably unveil genetic details not provided by DNA-only CGP. The integration of ctDNA detection further helped detect tumor-agnostic mutations and monitor treatment response.

背景：综合基因组分析（CGP）是一种时间和组织效率高的方法，有助于指导精确的肿瘤学。为了提高CGP的临床应用，我们研究了一种结合肿瘤DNA和mRNA分析以及液体活检ctDNA监测的新策略的性能。方法：同时提取604例12种肿瘤组织标本的基因组DNA和mRNA。肿瘤DNA采用高密度探针（HDP）的504基因面板进行靶向测序，并进行浅全基因组测序以分析基因组生物标志物。mRNA转录组分析用于进一步捕获融合变异，并使用我们的集成模型OriCUP预测起源组织（TOO），该算法在9889个样本上进行了训练，并在731个样本上进行了独立验证。在一组55例转移性肺癌患者中，采用肿瘤知情和肿瘤不可知的混合方法分析纵向血浆ctDNA，以预测无进展生存期（PFS）。结果：在所有生物标志物中，使用HDP的DNA测序在识别染色体、基因和外显子水平的拷贝数变化方面比标准面板设计具有更高的灵敏度。在参考样本中，单独使用DNA测序对融合变异的检出率比mRNA测序低20%，而两种方法的结合对于最大限度地提高临床FFPE样本的融合检出率至关重要。对于TOO，我们的OriCup模型对原发肿瘤的预测准确率为87.7%，对转移性肿瘤的预测准确率为81.4%。在55名肺癌患者中，ctDNA分析发现了11.5%的肿瘤不可知的可操作和耐药突变。ctDNA较基线减少50%以上的患者被归类为分子应答者，其PFS明显长于分子无应答者（HR = 9.42, 95% CI: 3.33-26.67, p）。结论：全面的基因组和转录组学分析可以可靠地揭示仅dna CGP无法提供的遗传细节。ctDNA检测的整合进一步帮助检测肿瘤不可知突变和监测治疗反应。

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引用次数: 0

A Phase II Pilot Study of Anti-PD-L1, Durvalumab, and a PARP Inhibitor, Olaparib in Patients With Metastatic Triple-Negative Breast Cancer With or Without Germline BRCA Mutation 抗pd - l1 Durvalumab和PARP抑制剂Olaparib在伴有或不伴有种系BRCA突变的转移性三阴性乳腺癌患者中的II期试点研究

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-12-08 DOI: 10.1002/cam4.71220

Takeo Fujii, Ashley Cimino-Mathews, Stanley Lipkowitz, Min-Jung Lee, Jayakumar Nair, Britanny Brooke Solarz, Alexandra Zimmer, Bernadette Redd, Elliot B. Levy, Shraddha Rastogi, Nahoko Sato, Ann McCoy, Seth M. Steinberg, Jung-Min Lee

Background

Immunostimulatory effects of PARP inhibitors could increase sensitivity to immune checkpoint inhibitors. The previous Phase II trial (MEDIOLA) reported clinical benefits of durvalumab and olaparib (D + O) in patients with germline BRCA-mutated (gBRCAm) HER2-negative metastatic breast cancer. Yet, the clinical activity of D + O in germline BRCA wild-type (gBRCAwt) triple-negative breast cancer (TNBC) remains unknown.

Methods

This single-arm Phase II study tested D + O in patients with metastatic TNBC. The primary objective was overall response rate (ORR). Secondary objectives were safety, disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Based on gBRCA status, patients were assigned to either gBRCAwt or gBRCAm cohort and were treated with D (1500 mg iv q4w) and O (300 mg twice a day orally). Pretreatment fresh tissues and serial blood samples were collected for correlative studies.

Results

Fifteen patients (12 gBRCAwt and 3 gBRCAm) were enrolled. gBRCAm and gBRCAwt cohorts are reported as a combined dataset because of small sample size due to COVID-19 and slow accrual. The median number of prior therapies was three (range 0–8). Among 14 RECIST-evaluable patients (11 gBRCAwt and 3 gBRCAm), ORR was 28.6% (3 gBRCAm and 1 gBRCAwt). DCR was 64.3% (3 gBRCAm and 6 gBRCAwt). The median PFS and OS were 3.6 months (95% confidence interval [CI]: 1.8–5.7) and 10.7 months (95% CI: 5.9–38.9), respectively. There is one gBRCAm patient with ongoing durable PR (67.4+ months). There was no new safety concern. CD83 expression on Types 1 and 2 conventional dendritic cells in blood at baseline was low in the patients with PFS ≥ 4 months compared to those with PFS < 4 months.

Conclusion

Our study demonstrated modest clinical benefits of D + O with ORR of 28.6% in subsets of heavily pretreated TNBC. Further detailed classification of DCs to understand the predictive role of DCs and prospective validation in a large cohort is required.

Trial Registration

ClinicalTrials.gov identifier: NCT02484404

背景：PARP抑制剂的免疫刺激作用可增加对免疫检查点抑制剂的敏感性。先前的II期试验（MEDIOLA）报告了durvalumab和olaparib （D + O）在种系brca突变（gBRCAm） her2阴性转移性乳腺癌患者中的临床益处。然而，D + O在种系BRCA野生型（gBRCAwt）三阴性乳腺癌（TNBC）中的临床活性尚不清楚。方法：这项单臂II期研究检测了转移性TNBC患者的D + O。主要目标是总有效率（ORR）。次要目标是安全性、疾病控制率（DCR）、无进展生存期（PFS）和总生存期（OS）。根据gBRCA状态，患者被分配到gbrcat或gBRCAm队列，并接受D （1500mg iv q4w）和O （300mg每日2次口服）治疗。采集预处理后的新鲜组织和连续血液样本进行相关性研究。结果：15例患者（12例gBRCAwt和3例gBRCAm）入组。由于COVID-19的样本量小且累积缓慢，因此将gBRCAm和gBRCAwt队列报告为组合数据集。既往治疗的中位数为3次（范围0-8）。在14例可recist评估的患者（11例gbrcat和3例gBRCAm）中，ORR为28.6%（3例gBRCAm和1例gbrcat）。DCR为64.3% （3 gBRCAm和6 gbrcat）。中位PFS和OS分别为3.6个月（95%可信区间[CI]: 1.8-5.7）和10.7个月（95% CI: 5.9-38.9）。有1例gBRCAm患者持续持久PR（67.4+月）。没有新的安全隐患。与PFS患者相比，PFS≥4个月的患者血液中1型和2型常规树突状细胞CD83在基线时的表达较低。结论：我们的研究表明，在重度预处理的TNBC亚群中，D + O的临床益处适度，ORR为28.6%。需要对dc进行进一步的详细分类，以了解dc的预测作用，并在大型队列中进行前瞻性验证。试验注册：ClinicalTrials.gov标识符：NCT02484404。

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引用次数: 0

HER2-Targeted Antibody-Drug Conjugate Toxicities in Breast Cancer 乳腺癌中her2靶向抗体-药物结合毒性

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-12-08 DOI: 10.1002/cam4.71415

Seohyuk Lee, Adriana M. Kahn, Mariya Rozenblit, Mridula A. George, Cristina Naranjo Ortiz, Maryam B. Lustberg

Background

HER2-targeted antibody-drug conjugates (ADCs) have dramatically advanced breast cancer outcomes. Two HER2-targeted ADCs, trastuzumab deruxtecan and trastuzumab emtansine, are currently approved for use in breast cancer, with > 60 other candidates under ongoing investigation.

Methods

In this report, we provide a narrative review of existing data underlying the current understanding of HER2-targeted ADC toxicities in breast cancer, highlighting both common and serious adverse events.

Results

When used as an adjuvant or neoadjuvant, first- or second-line agent, alone or in combination with another agent, trastuzumab emtansine has been commonly associated with epistaxis, fatigue, headache, nausea, and pyrexia across several clinical trials. Comparatively, trastuzumab deruxtecan has been commonly associated with alopecia, cytopenias, decreased appetite, fatigue, and gastrointestinal adverse effects.

Conclusion

Despite the demonstrated clinical benefits in breast cancer, diverse systemic and organ-specific adverse events, including dose-limiting toxicities, have been reported even at suboptimal therapeutic doses and pose significant barriers to pursuing dose escalations for maximizing therapeutic efficacy.

背景：her2靶向抗体-药物偶联物（adc）具有显著改善乳腺癌预后的作用。两种her2靶向adc，曲妥珠单抗德鲁西替康和曲妥珠单抗恩坦辛，目前已被批准用于乳腺癌，另有60种候选药物正在研究中。方法：在本报告中，我们对现有数据进行了叙述性回顾，这些数据基于目前对her2靶向ADC在乳腺癌中的毒性的理解，突出了常见和严重的不良事件。结果：在一些临床试验中，曲妥珠单抗emtansine作为辅助或新辅助、一线或二线药物，单独或与另一种药物联合使用时，通常与鼻出血、疲劳、头痛、恶心和发热有关。相比之下，曲妥珠单抗德鲁特康通常与脱发、细胞减少、食欲下降、疲劳和胃肠道不良反应有关。结论：尽管证明了乳腺癌的临床益处，但即使在次优治疗剂量下，也报告了多种系统性和器官特异性不良事件，包括剂量限制性毒性，这对追求剂量升级以最大化治疗效果构成了重大障碍。

{"title":"HER2-Targeted Antibody-Drug Conjugate Toxicities in Breast Cancer","authors":"Seohyuk Lee, Adriana M. Kahn, Mariya Rozenblit, Mridula A. George, Cristina Naranjo Ortiz, Maryam B. Lustberg","doi":"10.1002/cam4.71415","DOIUrl":"10.1002/cam4.71415","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>HER2-targeted antibody-drug conjugates (ADCs) have dramatically advanced breast cancer outcomes. Two HER2-targeted ADCs, trastuzumab deruxtecan and trastuzumab emtansine, are currently approved for use in breast cancer, with > 60 other candidates under ongoing investigation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this report, we provide a narrative review of existing data underlying the current understanding of HER2-targeted ADC toxicities in breast cancer, highlighting both common and serious adverse events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>When used as an adjuvant or neoadjuvant, first- or second-line agent, alone or in combination with another agent, trastuzumab emtansine has been commonly associated with epistaxis, fatigue, headache, nausea, and pyrexia across several clinical trials. Comparatively, trastuzumab deruxtecan has been commonly associated with alopecia, cytopenias, decreased appetite, fatigue, and gastrointestinal adverse effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Despite the demonstrated clinical benefits in breast cancer, diverse systemic and organ-specific adverse events, including dose-limiting toxicities, have been reported even at suboptimal therapeutic doses and pose significant barriers to pursuing dose escalations for maximizing therapeutic efficacy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 23","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12685761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145706857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-12-08 DOI: 10.1002/cam4.71401

Anna Fleischer, Magdalena Roll, Jan H. Frenking, Franziska Panther, Götz Gelbrich, Patrick-Pascal Strunz, Christine Riedhammer, Jessica Peter, Julia Mersi, Johannes Waldschmidt, Martin Kortüm, Hermann Einsele, Marc-S. Raab, Imad Maatouk, Leo Rasche

Background

Dysgeusia is a side effect of the anti-GPRC5DxCD3 bispecific antibody talquetamab (TAL), but other myeloma treatments, such as high-dose melphalan (MEL) with autologous stem cell transplantation (ASCT), are also known to alter taste perception in patients with multiple myeloma (MM). This study investigates the spectrum, prevalence and severity of dysgeusia in patients receiving TAL and MEL and compares the results with anti-BCMA bispecifics as a control for T-cell-engaging therapies.

Methods

Gustatory and olfactory performance was assessed in 87 MM patients divided into three treatment groups: TAL (n = 26), MEL/ASCT (n = 35), and BCMA bispecifics (n = 26). Evaluations included Taste Strips, Sniffin' Sticks Identification Test 16, and comprehensive questionnaires on taste perception, dietary issues, quality of life (QoL), mood, and treatment compliance.

Results

TAL-treated patients exhibited severe taste impairment, with 96.2% reporting marked declines. Taste alterations were also observed in patients receiving MEL/ASCT and BCMA bispecifics, though these were less pronounced, affecting 62.9% and 30.8% of cases, respectively. Xerostomia incidence was highest in the TAL group. Patients considering discontinuation of TAL (30%) cited taste alterations as the primary reason. MEL was associated with higher incidences of nausea, vomiting, and appetite loss.

Conclusion

TAL-associated taste disturbances have a major impact on patients and require further investigation and mitigation strategies. Enhanced patient support, proactive monitoring, and targeted interventions are critical to improving the well-being and adherence of MM patients.

背景：发音障碍是抗gprc5dxcd3双特异性抗体talquetamab （TAL）的副作用，但其他骨髓瘤治疗，如大剂量美伐兰（MEL）联合自体干细胞移植（ASCT），也已知会改变多发性骨髓瘤（MM）患者的味觉。本研究调查了接受TAL和MEL治疗的患者的谱系、患病率和严重程度，并将结果与抗bcma双特异性作为t细胞参与治疗的对照进行了比较。方法：将87例MM患者分为三个治疗组：TAL （n = 26）、MEL/ASCT （n = 35）和BCMA双特异性（n = 26），评估其味觉和嗅觉功能。评估包括味觉条、嗅探棒识别测试16，以及关于味觉、饮食问题、生活质量（QoL）、情绪和治疗依从性的综合问卷。结果：tal治疗的患者表现出严重的味觉障碍，96.2%的患者报告显着下降。在接受MEL/ASCT和BCMA双特异性治疗的患者中也观察到味觉改变，尽管这些变化不太明显，分别影响62.9%和30.8%的病例。TAL组口干发生率最高。考虑停药的患者（30%）认为味觉改变是主要原因。MEL与恶心、呕吐和食欲减退的发生率较高有关。结论：tal相关的味觉障碍对患者有重大影响，需要进一步调查和缓解策略。加强患者支持、主动监测和有针对性的干预对于改善MM患者的福祉和依从性至关重要。

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引用次数: 0

TMEM106A as a Macrophage-Associated Biomarker of Prognosis in IDH-Wildtype Glioma: Integrative Multi-Omics and Spatial Analyses TMEM106A作为idh野生型胶质瘤巨噬细胞相关的预后生物标志物：综合多组学和空间分析

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-12-07 DOI: 10.1002/cam4.71454

Wen-Shin Song, Pei-Chi Chang, Dueng-Yuan Hueng, Yao-Feng Li

Introduction

Gliomas remain aggressive despite current therapies, highlighting the urgent need for new biomarkers and targets. Transmembrane protein 106A (TMEM106A), implicated as a tumor suppressor in various cancers, has an unclear role in gliomas. We hypothesized that TMEM106A expression associates with tumor aggressiveness and may serve as a prognostic, microenvironmental biomarker.

Methods

We integrated TCGA and CGGA bulk RNA-seq, single-cell (GSE131928, GSE89567), spatial (Ivy Atlas, Visium), and immunohistochemistry (n = 79) to evaluate TMEM106A. Differential expression used limma. Survival used Kaplan–Meier and multivariable Cox models. Immune contexture used a 12-cell-state deconvolution and CIBERSORT. GSEA assessed hallmark pathways. Drug sensitivity was inferred using pRRophetic. Immunotherapy modeling combined TCGA expression with TCIA immunophenoscore and PD-L1.

Results

(1) TMEM106A mRNA is significantly upregulated in high-grade gliomas compared to lower-grade gliomas and normal brain. (2) In IDH-wildtype tumors, differential analyses highlight roles of TMEM106A and TMEM106C; high expression links to poorer prognosis. (3) TMEM106A is an independent prognostic factor associated with aggressive behavior, especially in IDH-wildtype astrocytomas. (4) Upregulation is confirmed by immunohistochemistry. (5) High TMEM106A associates with pro-inflammatory signatures and higher inferred fractions of myeloid cells and granulocytes. (6) Single-cell RNA-seq shows enrichment in myeloid lineages, and (7) CIBERSORT shows modest positive correlations with polarized macrophage signatures. (8) Spatial transcriptomics shows higher TMEM106A in myeloid-rich regions, consistent with a microenvironmental readout. (9) In IDH-wildtype tumors, pRRophetic predicts lower IC50 for multiple targeted agents in TMEM106A-high tumors. (10) TMEM106A-high IDH-wildtype tumors show higher IPS only when PD-1 is “on,” suggesting a context-dependent, inflamed-but-suppressed state.

Conclusion

TMEM106A independently predicts survival and correlates with myeloid-enriched transcriptional states in gliomas. Given its high expression in myeloid lineages in single-cell data, bulk upregulation is potentially driven by myeloid infiltration rather than tumor-cell intrinsic mechanisms. All findings are correlative; prospective studies are needed before any clinical use is considered.

尽管目前的治疗方法，胶质瘤仍然具有侵袭性，强调迫切需要新的生物标志物和靶点。跨膜蛋白106A （TMEM106A）在多种癌症中作为肿瘤抑制因子，在胶质瘤中的作用尚不清楚。我们假设TMEM106A表达与肿瘤侵袭性相关，并可能作为预后的微环境生物标志物。方法：采用TCGA和CGGA bulk RNA-seq、单细胞（GSE131928、GSE89567）、空间（Ivy Atlas、Visium）和免疫组织化学（n = 79）对TMEM106A进行评价。微分表达式使用了limma。生存率采用Kaplan-Meier和多变量Cox模型。免疫环境使用12细胞状态反卷积和CIBERSORT。GSEA评估了标志通路。使用prophytic推断药物敏感性。免疫治疗模型结合TCGA表达、TCIA免疫表型评分和PD-L1。结果：(1)与低级别脑胶质瘤和正常脑相比，TMEM106A mRNA在高级别脑胶质瘤中显著上调。(2)在idh野生型肿瘤中，差异分析突出了TMEM106A和TMEM106C的作用；高表达与预后较差有关。(3) TMEM106A是与侵袭行为相关的独立预后因素，尤其是在idh野生型星形细胞瘤中。(4)免疫组化证实上调。(5)高TMEM106A与促炎特征和更高的髓细胞和粒细胞推测分数相关。(6)单细胞RNA-seq显示髓系谱系富集，(7)CIBERSORT显示与极化巨噬细胞特征适度正相关。(8)空间转录组学显示，在骨髓丰富的区域TMEM106A较高，与微环境读数一致。(9)在idh野生型肿瘤中，prorophetic预测多种靶向药物在tmem106a高水平肿瘤中的IC50较低。（10） tmem106a高idh野生型肿瘤只有在PD-1“开启”时才表现出更高的IPS，这表明这是一种依赖于环境、炎症但抑制的状态。结论：TMEM106A独立预测胶质瘤的生存，并与髓细胞富集的转录状态相关。鉴于其在单细胞髓系中的高表达，大量上调可能是由髓系浸润而不是肿瘤细胞内在机制驱动的。所有发现都是相关的；在考虑任何临床应用之前，需要进行前瞻性研究。

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引用次数: 0

The Burden of Pancreatic Cancer in Five East Asian Countries From 1990 to 2021 and Its Prediction up to 2036: A Systemic Analysis of the Global Burden of Diseases Study 2021 1990年至2021年东亚五国胰腺癌负担及其预测：2021年全球疾病负担研究的系统分析

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-12-07 DOI: 10.1002/cam4.70656

Tianhao Guo, Wenjian Zhu, Yifan Hui, Yuhan Wang, Tingting Zhou, Weixing Shen, Liu Li, Yu Yang, Haibo Cheng

Background

Pancreatic cancer (PC) presents a significant challenge for prevention and treatment, posing a serious threat to the health and lives of patients. The five East Asian countries (China, Japan, North Korea, South Korea, and Mongolia) represent one of the most significant regions globally in terms of PC burden.

Methods

We retrieved data from the Global Burden of Disease (GBD) Study 2021 regarding the prevalence, incidence, mortality, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life years (DALYs) associated with PC in these five East Asian countries from 1990 to 2021. We employed joinpoint, age-period-cohort (APC), and decomposition analysis methods to assess the epidemiological characteristics of PC. To project the future burden of PC through 2036, we applied two prediction models: Autoregressive Integrated Moving Average (ARIMA) and Bayesian age-period-cohort (BAPC) models.

Results

China recorded the highest incidence, prevalence, mortality, YLLs, YLDs, and DALYs among the five East Asian countries in both 1990 and 2021. Japan exhibited the highest age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized prevalence rate (ASPR), and age-standardized YLDs rate in both 1990 and 2021. Mongolia experienced significant increases in the number and rates of incidence, prevalence, death, YLLs, YLDs, and DALYs from 1990 to 2021. The age group with the highest prevalence, incidence, mortality, YLDs, YLLs, and DALYs rates across the five East Asian countries was consistently those aged 70 and older. The incidence rate across the five countries is influenced by aging populations, surpassing global averages. Projections for 2030 and 2036 suggest that Japan will have the highest ASPR (13.23 in 2030 and 13.85 in 2036), ASIR (12.14 in 2030 and 12.53 in 2036), and ASMR (10.97 in 2030 and 11.39 in 2036) among the countries.

Conclusion

The disease burden of PC in the five East Asian countries has steadily increased over the past three decades, particularly among older adults due to population aging.

背景：胰腺癌（Pancreatic cancer， PC）对患者的健康和生命构成严重威胁，是预防和治疗的重大挑战。五个东亚国家（中国、日本、朝鲜、韩国和蒙古）是全球PC负担最严重的地区之一。方法：我们从全球疾病负担（GBD）研究2021中检索数据，包括1990年至2021年这五个东亚国家与PC相关的患病率、发病率、死亡率、残疾生活年数（YLDs）、生命损失年数（YLLs）和残疾调整生命年（DALYs）。我们采用结合点、年龄-时期-队列（APC）和分解分析方法来评估PC的流行病学特征。为了预测到2036年的未来PC负担，我们应用了两种预测模型：自回归综合移动平均（ARIMA）和贝叶斯年龄-时期-队列（BAPC）模型。结果：1990年和2021年，中国的发病率、患病率、死亡率、年活龄、年活龄和残疾活龄在东亚五国中均为最高。1990年和2021年，日本的年龄标准化发病率（ASIR）、年龄标准化死亡率（ASMR）、年龄标准化患病率（ASPR）和年龄标准化YLDs率均最高。从1990年到2021年，蒙古的发病率、流行率、死亡率、生命周期、生命周期和生命周期均显著增加。在东亚五个国家中，患病率、发病率、死亡率、生命周期、生命周期和伤残调整生命年比率最高的年龄组始终是70岁及以上的年龄组。这五个国家的发病率受到人口老龄化的影响，超过了全球平均水平。对2030年和2036年的预测表明，日本将拥有最高的ASPR（2030年为13.23,2036年为13.85）、ASIR（2030年为12.14,2036年为12.53）和ASMR（2030年为10.97,2036年为11.39）。结论：东亚五国的PC疾病负担在过去三十年中稳步增加，特别是在老年人中，由于人口老龄化。

{"title":"The Burden of Pancreatic Cancer in Five East Asian Countries From 1990 to 2021 and Its Prediction up to 2036: A Systemic Analysis of the Global Burden of Diseases Study 2021","authors":"Tianhao Guo, Wenjian Zhu, Yifan Hui, Yuhan Wang, Tingting Zhou, Weixing Shen, Liu Li, Yu Yang, Haibo Cheng","doi":"10.1002/cam4.70656","DOIUrl":"10.1002/cam4.70656","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pancreatic cancer (PC) presents a significant challenge for prevention and treatment, posing a serious threat to the health and lives of patients. The five East Asian countries (China, Japan, North Korea, South Korea, and Mongolia) represent one of the most significant regions globally in terms of PC burden.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrieved data from the Global Burden of Disease (GBD) Study 2021 regarding the prevalence, incidence, mortality, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life years (DALYs) associated with PC in these five East Asian countries from 1990 to 2021. We employed joinpoint, age-period-cohort (APC), and decomposition analysis methods to assess the epidemiological characteristics of PC. To project the future burden of PC through 2036, we applied two prediction models: Autoregressive Integrated Moving Average (ARIMA) and Bayesian age-period-cohort (BAPC) models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>China recorded the highest incidence, prevalence, mortality, YLLs, YLDs, and DALYs among the five East Asian countries in both 1990 and 2021. Japan exhibited the highest age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized prevalence rate (ASPR), and age-standardized YLDs rate in both 1990 and 2021. Mongolia experienced significant increases in the number and rates of incidence, prevalence, death, YLLs, YLDs, and DALYs from 1990 to 2021. The age group with the highest prevalence, incidence, mortality, YLDs, YLLs, and DALYs rates across the five East Asian countries was consistently those aged 70 and older. The incidence rate across the five countries is influenced by aging populations, surpassing global averages. Projections for 2030 and 2036 suggest that Japan will have the highest ASPR (13.23 in 2030 and 13.85 in 2036), ASIR (12.14 in 2030 and 12.53 in 2036), and ASMR (10.97 in 2030 and 11.39 in 2036) among the countries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The disease burden of PC in the five East Asian countries has steadily increased over the past three decades, particularly among older adults due to population aging.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 23","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12683073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pretreatment Amide Proton Transfer-Weighted Imaging Histogram Analysis Combined With ER-Negative and HER2-Positive Expression Predicts Pathologic Complete Response After Neoadjuvant Chemotherapy in Breast Cancer 预处理酰胺质子转移加权成像直方图分析联合er阴性和her2阳性表达预测乳腺癌新辅助化疗后病理完全缓解。

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-12-07 DOI: 10.1002/cam4.71420

Mingzhe Xu, Dongqiu Shan, Xuejun Chen, Renzhi Zhang, Chunmiao Xu, Jing Li, Zhiwei Shen, Yue Wu, Jinrong Qu

Purpose

To evaluate the predictive value of pre-treatment histogram analysis using APTWI, diffusion-weighted imaging (DWI), and early contrast-enhanced silhouette imaging in determining pathological complete response (pCR) post-NAC in breast cancer, and to investigate whether combining immunohistochemical indicators enhances predictive accuracy.

Materials and Methods

A retrospective continuous collection of 108 females with breast cancer who underwent NAC and pre-treatment APTWI, DWI, and dynamic contrast-enhanced imaging at our hospital. Clinical, MRI imaging, and pathological characteristics were analyzed for patients. NAC response was divided into pCR and non-pCR. Tumor segmentation and histogram feature extraction were performed on APT, ADC, and early contrast-enhanced silhouette images, and combined them with clinical features to construct an NAC efficacy prediction model. Diagnostic performance was assessed using receiver operating characteristic curves, with DeLong's test employed to compare areas under the curve (AUC).

Results

In pCR group, mean, root-mean-square deviation, and 5th, 10th, 15th, 25th, 50th, 75th, 85th percentile of MTRasym, along with 1st percentiles of ADC were significantly higher in the pCR group than in the non-pCR group (p < 0.05). Conversely, the interquartile range of MTRasym and 10th percentiles of ADC were significantly lower in the pCR group (p < 0.05). ER-negative, HER2-positive expression, and 5th percentile MTRasym value were identified as independent predictors of pCR post-NAC (odds ratios, 0.16, 7.25, and 1.35, respectively). The combined diagnostic model demonstrated an AUC of 0.844, significantly outperforming individual parameters (p < 0.05).

Conclusion

Pre-treatment histogram analysis of MTRasym values derived from APTWI provides significant predictive value for pCR post-NAC in breast cancer. The combined diagnostic model incorporating APTWI with ER and HER2 expression status further enhances diagnostic performance.

目的：评价应用APTWI、弥散加权成像（diffusion weighted imaging， DWI）和早期增强剪影成像进行治疗前直方图分析对乳腺癌nac后病理完全反应（pathological complete response, pCR）的预测价值，并探讨联合免疫组化指标是否能提高预测准确性。材料与方法：回顾性连续收集我院行NAC及治疗前APTWI、DWI、动态增强成像的女性乳腺癌患者108例。分析患者的临床、MRI及病理特征。NAC反应分为pCR反应和非pCR反应。对APT、ADC和早期增强剪影图像进行肿瘤分割和直方图特征提取，并结合临床特征构建NAC疗效预测模型。采用受试者工作特征曲线评估诊断性能，采用DeLong试验比较曲线下面积（AUC）。结果：pCR组MTRasym的均值、均方根偏差、5、10、15、25、50、75、85百分位数以及ADC的1百分位数均显著高于非pCR组(p)。结论：APTWI提取的MTRasym值的治疗前直方图分析对乳腺癌pCR后nac有显著的预测价值。将APTWI与ER和HER2表达状态结合的联合诊断模型进一步提高了诊断效能。

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引用次数: 0

Dualistic Roles of High Mobility Group Box 1 in Cancer and Inflammation 高迁移率组1在癌症和炎症中的双重作用。

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-12-07 DOI: 10.1002/cam4.71455

Wen Zeng, Xu Zhang, Yulu Jiang, Yuxiang Luo, Zuao Wang, Xiaohong Du, Leifeng Chen

<div> <section> <h3> Background</h3> <p>The High Mobility Group Box 1 (HMGB1) protein, a member of the HMG family, plays a crucial role in both cancer progression and inflammatory responses. HMGB1 can act as a damage-associated molecular pattern (DAMP) to activate immune responses and modulate inflammation. Its dualistic roles in promoting and inhibiting tumor growth, as well as its involvement in DNA repair and drug resistance, make it a key target for understanding and treating cancer and inflammatory diseases.</p> </section> <section> <h3> Objective</h3> <p>This review aims to explore the dualistic roles of HMGB1 in cancer and inflammation, focusing on its pro-inflammatory and anti-inflammatory functions in the tumor microenvironment, its impact on DNA damage repair and tumor drug resistance, and its potential as a therapeutic target for cancer and inflammatory diseases.</p> </section> <section> <h3> Methods</h3> <p>We conducted a comprehensive review of the literature on HMGB1, analyzing its structural features, biological functions, and mechanisms of action in various pathological contexts. We also examined the impact of HMGB1 on tumor progression, immune responses, and metabolic reprogramming in cancer cells, as well as its role in inflammatory signaling pathways.</p> </section> <section> <h3> Results</h3> <p>HMGB1 exhibits both oncogenic and tumor-suppressive effects in cancer. It promotes tumor growth, metastasis, and immune evasion through mechanisms such as shaping the tumor microenvironment, driving metabolic reprogramming, and inducing drug resistance. Conversely, HMGB1 can enhance anti-tumor immunity by activating dendritic cells and T cells. In inflammation, HMGB1 acts as a DAMP, activating immune responses via receptors like RAGE and TLR4. Its redox state and subcellular localization determine its proinflammatory or anti-inflammatory functions. Targeting HMGB1 has shown promise in preclinical and clinical studies, with potential applications in anti-cancer and anti-inflammatory therapies.</p> </section> <section> <h3> Conclusion</h3> <p>The dualistic roles of HMGB1 in cancer and inflammation highlight its complexity and potential as a therapeutic target. Future research should focus on elucidating the context-specific mechanisms of HMGB1, developing precision-targeted therapies to modulate its multifunctional activities, and translating these findings into clinical practice to improve patient outcomes.</p> </section>

背景：高迁移率组框1 （HMGB1）蛋白是HMG家族的成员，在癌症进展和炎症反应中起着至关重要的作用。HMGB1可以作为一种损伤相关分子模式（DAMP）激活免疫反应并调节炎症。它在促进和抑制肿瘤生长方面的双重作用，以及参与DNA修复和耐药性，使其成为了解和治疗癌症和炎症性疾病的关键靶点。目的：本文旨在探讨HMGB1在肿瘤和炎症中的双重作用，重点探讨其在肿瘤微环境中的促炎和抗炎功能，对DNA损伤修复和肿瘤耐药的影响，以及其作为癌症和炎症疾病治疗靶点的潜力。方法：我们对有关HMGB1的文献进行了全面的综述，分析其结构特征、生物学功能以及在各种病理情况下的作用机制。我们还研究了HMGB1对肿瘤进展、免疫反应和癌细胞代谢重编程的影响，以及它在炎症信号通路中的作用。结果：HMGB1在肿瘤中具有致癌和抑瘤双重作用。它通过塑造肿瘤微环境、驱动代谢重编程和诱导耐药等机制促进肿瘤生长、转移和免疫逃避。相反，HMGB1可以通过激活树突状细胞和T细胞增强抗肿瘤免疫。在炎症中，HMGB1作为一种DAMP，通过RAGE和TLR4等受体激活免疫反应。其氧化还原状态和亚细胞定位决定了其促炎或抗炎功能。靶向HMGB1在临床前和临床研究中显示出良好的前景，在抗癌和抗炎治疗中具有潜在的应用前景。结论：HMGB1在肿瘤和炎症中的双重作用突出了其复杂性和作为治疗靶点的潜力。未来的研究应侧重于阐明HMGB1的环境特异性机制，开发精确靶向治疗来调节其多功能活动，并将这些发现转化为临床实践以改善患者预后。

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引用次数: 0

Overexpressed CD24 and CD47 Indicate a Worse Prognosis in Cervical Cancer CD24和CD47过表达提示宫颈癌预后较差

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine

Pub Date : 2025-12-07 DOI: 10.1002/cam4.71443

Min Yu, Mengdong Ni, Fei Xu, Chi Fang, Jiajia Li, Xiaohua Wu, Guihao Ke

Background

Two antiphagocytic (“don't eat me”) signals that allow tumor immune evasion have been discovered, including CD24 and CD47. This study explored the association between CD24/CD47 expression and macrophage infiltration and clinical outcomes in cervical cancer.

Methods

RNA expression and survival data of the Cancer Genome Atlas (TCGA) cohort were extracted from OncoLnc. The macrophage infiltration level was calculated using xCell, TIMER, and ImmuCellAI. The expression of CD24 and CD47 was detected by immunohistochemistry in tissue microarrays composed of 130 clinical cervical cancer specimens from Fudan University Shanghai Cancer Center (FUSCC). Patients' medical records were also retrospectively assessed to correlate demographic and survival data.

Results

Expression levels of both CD24 and CD47 in the cancer population were higher than those in the normal population. Patients with high CD24 expression had poorer survival than those with low CD24 expression in the TCGA and FUSCC cervical cancer cohorts. Although CD47 alone was not statistically significant in predicting outcomes, patients with high CD47 and low CD11c expression, a specific marker of M1-polarized macrophages, exhibited worse survival in the TCGA cohort.

Conclusions

Our study implies that high CD24 expression is an important predictor of a worse prognosis, and CD24 blockade might have therapeutic potential for the treatment of cervical cancer. High expression levels of CD47 and low M1-polarized macrophage infiltration predict a worse prognosis.

背景：已经发现了两种允许肿瘤免疫逃避的抗吞噬（“不要吃我”）信号，包括CD24和CD47。本研究探讨CD24/CD47表达、巨噬细胞浸润与宫颈癌临床结局的关系。方法：提取肿瘤基因组图谱（TCGA）队列的RNA表达和生存数据。使用xCell、TIMER和ImmuCellAI计算巨噬细胞浸润水平。应用免疫组织化学方法检测了130例复旦大学上海肿瘤中心宫颈癌临床标本组织微阵列中CD24和CD47的表达。患者的医疗记录也被回顾性评估，以关联人口统计学和生存数据。结果：肿瘤人群中CD24和CD47的表达水平均高于正常人群。在TCGA和FUSCC宫颈癌队列中，CD24高表达患者的生存率低于CD24低表达患者。虽然CD47在预测预后方面没有统计学意义，但在TCGA队列中，高CD47和低CD11c（一种m1极化巨噬细胞的特异性标志物）表达的患者表现出更差的生存率。结论：本研究提示CD24高表达是宫颈癌预后不良的重要预测因子，CD24阻断可能具有治疗宫颈癌的潜力。CD47高表达和低m1极化巨噬细胞浸润预示着较差的预后。

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引用次数: 0