Translational Oncology最新文献_第2页

Piperlongumine suppresses YAP-ET-1-CXCL2 signaling to modulates aggressiveness of triple-negative breast cancer cells 胡椒隆明抑制YAP-ET-1-CXCL2信号通路调节三阴性乳腺癌细胞的侵袭性

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2026-04-01 Epub Date: 2026-02-12 DOI: 10.1016/j.tranon.2026.102700

Ming-Yi Hsieh , Ching-Chieh Yang , Wen-Jing Hsu , Zei-Wei Liu , Hsin-Ying Lu , Ming-Chen Chiang , Cheng-Jui Huang , Ching-Yun Liao , Cheng-Wei Lin , Pei-Wei Shueng

Triple-negative breast cancer (TNBC) is characterized by highly aggressive and metastatic properties, and appropriate molecular targets and therapeutics for effective treatment remain limited. In the present study, by using RNA sequencing (RNA-Seq) analysis of upregulated genes expression in metastatic breast tumor cells, we identified that the Yes-associated protein (YAP)- endothelin (ET)-1 signaling axis were concomitantly elevated in metastatic breast tumor tissues and their overexpression conferred poor survival outcomes, particular in patients with TNBC. Moreover, we identified that piperlongumine (PL), a naturally occurring small molecule derived from long pepper, exhibits potent antitumor activities in TNBC cells. PL effectively suppressed cell proliferation, promoted apoptosis, and inhibited tumor migration and invasion. Furthermore, PL activates Hippo signaling which was accompanied by downregulation of YAP level. Consequently, PL suppressed YAP signaling to further downregulate ET-1 expression. Additionally, ET-1 elevation was identified to be associated with cancer-associated fibroblast (CAF) and C-X-C motif chemokine ligand 2 (CXCL2) signature, while treatment with PL significantly downregulated CXCL2 expression and consequently decreased CAF activation. Finally, PL treatment significantly inhibited in vivo tumor growth and suppressed CAF infiltration in the tumor microenvironment. Together, these findings demonstrated that PL might be a promising chemotherapeutic agent to efficiently target YAP-ET-1-CXCL2 signaling and thus has therapeutic potential for TNBC patients.

三阴性乳腺癌（TNBC）具有高度侵袭性和转移性，适当的分子靶点和有效治疗方法仍然有限。在本研究中，通过对转移性乳腺肿瘤细胞中上调基因表达的RNA测序（RNA- seq）分析，我们发现，yes相关蛋白(YAP)-内皮素(ET)-1信号轴在转移性乳腺肿瘤组织中同时升高，其过表达导致生存结果较差，特别是在TNBC患者中。此外，我们发现胡椒明（PL）是一种天然存在的从长辣椒中提取的小分子，在TNBC细胞中表现出有效的抗肿瘤活性。PL能有效抑制细胞增殖，促进细胞凋亡，抑制肿瘤迁移和侵袭。此外，PL激活Hippo信号，并伴随YAP水平下调。因此，PL抑制YAP信号进一步下调ET-1的表达。此外，ET-1升高被确定与癌症相关成纤维细胞（CAF）和C-X-C基序趋化因子配体2 （CXCL2）特征相关，而PL治疗显著下调CXCL2表达，从而降低CAF激活。最后，PL处理显著抑制体内肿瘤生长，抑制肿瘤微环境中CAF的浸润。总之，这些发现表明，PL可能是一种有前景的化疗药物，可以有效靶向YAP-ET-1-CXCL2信号传导，因此对TNBC患者具有治疗潜力。

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引用次数: 0

An unfavorable biologic profile associated with decreased overall survival and cancer-specific survival in non-metastatic breast cancer: A latent class analysis 在非转移性乳腺癌中，与总生存率和癌症特异性生存率降低相关的不利生物学特征：一项潜在分类分析

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2026-04-01 Epub Date: 2026-02-13 DOI: 10.1016/j.tranon.2026.102694

Claire Falandry , Sigrid Hatse , Barbara Brouwers , Cindy Kenis , Ann Smeets , Patrick Neven , Charlotte Cuerq , Frederic Pamoukdjian , Karim Chikh , Hans Wildiers

Background

Chronological age is an imperfect proxy for risk assessment in geriatric oncology. There is an urgent need for an objective, easily measurable biological aging signature to refine patient stratification and personalize therapeutic decisions.

Methods

We analyzed a panel of seven aging-related biomarkers (including markers of inflammation, anabolic reserve, and telomere status) in 244 nonmetastatic breast cancer patients from two age groups (“Old”, ≥70 years, N = 162; “Young”, ≤60 years, N = 82). We used Latent Class Analysis (LCA) to integrate these markers and identify distinct biological risk profiles. These profiles were then evaluated for their association with Overall Survival (OS) and Cancer-Specific Death (CSD) via Competing Risk Analysis.

Results

LCA identified two patient profiles. The Unfavorable Biologic Profile (56.1% of the cohort) was defined by a triad of high MCP-1, high Chitinase activity, and low IGF-1. This profile was strongly associated with poorer OS (Age-adjusted HR=1.82, p = 0.018). Crucially, 15% of chronologically “Young” patients were assigned to this high-risk profile, while 23% of “Old” patients were assigned to the Favorable Profile. Furthermore, the Unfavorable Profile was more strongly and specifically associated with CSD (Subdistribution HR: 2.05, p = 0.012) than with Non-Cancer Death.

Conclusion

Our results delineate an unfavorable, trans-chronological biological profile that identifies patients with low host reserve, largely driven by inflammaging and catabolism. This integrated signature provides a robust, objective screening tool to identify biologically frail patients, validating the need for Comprehensive Geriatric Assessment (CGA) and biomarker-guided therapeutic de-escalation (e.g., avoiding adjuvant chemotherapy) to improve individualized outcomes in oncology.Trial registration: BS32220096117.

背景：在老年肿瘤中，实足年龄是一个不完美的风险评估指标。迫切需要一种客观的、易于测量的生物衰老特征来完善患者分层和个性化治疗决策。方法我们分析了244例来自两个年龄组（老年，≥70岁，N = 162；年轻，≤60岁，N = 82）的非转移性乳腺癌患者的7种衰老相关生物标志物（包括炎症标志物、合成代谢储备和端粒状态）。我们使用潜在类别分析（LCA）来整合这些标记物并确定不同的生物风险概况。然后通过竞争风险分析评估这些概况与总生存期（OS）和癌症特异性死亡（CSD）的相关性。结果slca鉴定出两种患者特征。不利的生物学特征（56.1%的队列）由高MCP-1，高几丁质酶活性和低IGF-1三重特征定义。这种情况与较差的OS密切相关（年龄调整HR=1.82, p = 0.018）。至关重要的是，15%的“年轻”患者被分配到高风险组，而23%的“年老”患者被分配到有利组。此外，与非癌症死亡相比，不良概况与CSD的相关性更强、更特异（亚分布HR: 2.05, p = 0.012）。结论：我们的研究结果描述了一个不利的，跨时间的生物学特征，确定了低宿主储备的患者，主要由炎症和分解代谢驱动。这种集成的特征提供了一个强大的、客观的筛选工具来识别生物学上虚弱的患者，验证了综合老年评估（CGA）和生物标志物引导的治疗降级（例如，避免辅助化疗）的必要性，以改善肿瘤学的个体化结果。试验注册号：BS32220096117。

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引用次数: 0

A review of treatment strategies for elderly patients with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia 老年费城染色体阴性b细胞急性淋巴细胞白血病的治疗策略综述

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2026-04-01 Epub Date: 2026-02-13 DOI: 10.1016/j.tranon.2026.102706

Kaihang Shi, Gaoxiang Wang, Xueyan Sun

The treatment of elderly patients with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (pH⁻ B-ALL) remains challenging because of the high frequency of adverse genetic features, common comorbidities, and significant treatment-related toxicities, which collectively limit the efficacy of conventional chemotherapy and result in poor long-term survival. Recent years have witnessed the emergence of novel targeted agents and immunotherapies, substantially improving the therapeutic outlook for this population. This review summarizes recent advances in the application of low-intensity chemotherapy, CD19/CD22-targeting antibodies such as blinatumomab and inotuzumab ozogamicin, the BCL-2 inhibitor venetoclax, and chimeric antigen receptor (CAR) T-cell therapy for elderly pH⁻ B-ALL patients. Clinical studies indicate that these strategies can increase remission rates and survival while reducing treatment-related toxicity, offering particular benefit to older patients who are unsuitable for intensive chemotherapy. Future efforts should focus on optimizing combination and sequential regimens, as well as personalizing treatment approaches to further improve efficacy and safety.

费城染色体阴性b细胞急性淋巴细胞白血病（pH - B-ALL）的老年患者的治疗仍然具有挑战性，因为不良遗传特征的频率高，常见的合共病和显著的治疗相关毒性，这些共同限制了传统化疗的疗效，导致长期生存率低。近年来，新的靶向药物和免疫疗法的出现，大大改善了这一人群的治疗前景。本文综述了低强度化疗、靶向CD19/ cd22的抗体（如blinatumomab和inotuzumab ozogamicin）、BCL-2抑制剂venetoclax和嵌合抗原受体（CAR） t细胞治疗老年pH - B-ALL患者的最新进展。临床研究表明，这些策略可以提高缓解率和生存率，同时减少治疗相关的毒性，对不适合强化化疗的老年患者特别有益。未来的工作应侧重于优化组合和顺序方案，以及个性化治疗方法，以进一步提高疗效和安全性。

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引用次数: 0

Application of radiomics in head and neck squamous cell carcinoma 放射组学在头颈部鳞状细胞癌中的应用。

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2026-04-01 Epub Date: 2026-02-07 DOI: 10.1016/j.tranon.2026.102689

Siyi Wu , Zaiyu Wang , Yu Zhang , Qi Chen , Honghao Liu , Yedong Shen , Juxiong Xiao , Luqing Zhao , Yitao Mao

Head and neck squamous cell carcinoma (HNSCC) is the most prevalent histopathological subtype of head and neck malignancies. Owing to the lack of early specific symptoms, the majority of patients are diagnosed at intermediate or advanced stages, which is associated with an unfavorable prognosis and a substantial decline in quality of life. Radiomics, which leverages large-scale medical imaging data, enables the extraction of high-dimensional quantitative features through advanced image analysis, thereby providing deeper insights into tumor biology. In this review, we summarize recent advances in radiomics for the diagnosis, prognostic prediction, and evaluation of treatment-related toxicity in HNSCC. Furthermore, we highlight emerging applications of radiomics in genomics and proteomics, illustrating the associations between tumor molecular phenotypes and imaging-derived features. Finally, we discuss the challenges related to feature standardization and reproducibility, and outline the key limitations of current radiomics studies.

头颈部鳞状细胞癌（HNSCC）是头颈部恶性肿瘤中最常见的组织病理学亚型。由于缺乏早期特异性症状，大多数患者被诊断为中晚期，这与预后不良和生活质量大幅下降有关。放射组学利用大规模医学成像数据，通过先进的图像分析提取高维定量特征，从而对肿瘤生物学提供更深入的了解。在这篇综述中，我们总结了放射组学在HNSCC的诊断、预后预测和治疗相关毒性评估方面的最新进展。此外，我们强调放射组学在基因组学和蛋白质组学中的新兴应用，说明肿瘤分子表型和成像衍生特征之间的关联。最后，我们讨论了与特征标准化和可重复性相关的挑战，并概述了当前放射组学研究的主要局限性。

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引用次数: 0

Integrated multi-omics analysis of prognostic model and immune microenvironment in intrahepatic cholangiocarcinoma 肝内胆管癌预后模型和免疫微环境的综合多组学分析。

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2026-03-01 Epub Date: 2026-01-19 DOI: 10.1016/j.tranon.2026.102675

Xi Li , Yixian Wang , Xiangbao Yin , Junwen Hu , Hongcheng Lu , Die Li , Mingming Wu

Background

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive malignancy originating from the epithelial lining of second-order bile ducts. Despite advances in immunotherapy, which underscore the pivotal roles of T-cell dynamics and tumor microenvironment (TME) remodeling in anti-tumor immunity, iCCA remains a clinical challenge due to its rapid progression. Consequently, there is a pressing need for integrated multi-omics approaches to elucidate the immune landscape of iCCA and guide effective precision immunotherapy.

Methods

To comprehensively characterize iCCA, we integrated single-cell RNA-seq data for microenvironment analysis and bulk RNA-seq cohorts for prognostic model construction using machine learning, followed by external validation and functional experimental verification of key genes.

Results

Integrated single-cell and spatial transcriptomic analysis of iCCA uncovered interacting epithelial-fibroblast subpopulations and guided the machine learning-based derivation of a five-gene prognostic signature. Furthermore, spatial transcriptomics confirmed the physical co-localization between SPP1+ Macrophage and NDRG1+ CAF. Finally, functional experiments established that MT1X, a gene highly expressed in iCCA, drives tumor proliferation, migration, and invasion.

Conclusion

This study establishes a prognostic model based on five key genes and elucidates their role in the immunosuppressive TME. MT1X was validated as a pro-tumorigenic factor, highlighting its potential as a therapeutic target.

背景：肝内胆管癌（iCCA）是一种起源于二级胆管上皮的侵袭性恶性肿瘤。尽管免疫治疗的进步强调了t细胞动力学和肿瘤微环境（TME）重塑在抗肿瘤免疫中的关键作用，但由于其快速进展，iCCA仍然是一个临床挑战。因此，迫切需要整合多组学方法来阐明iCCA的免疫景观并指导有效的精确免疫治疗。方法：为了全面表征iCCA，我们整合了单细胞RNA-seq数据进行微环境分析，并利用机器学习整合了大量RNA-seq队列进行预后模型构建，随后对关键基因进行外部验证和功能实验验证。结果：iCCA的综合单细胞和空间转录组学分析揭示了相互作用的上皮-成纤维细胞亚群，并指导了基于机器学习的五基因预后标记的推导。此外，空间转录组学证实了SPP1+巨噬细胞和NDRG1+ CAF之间的物理共定位。最后，功能实验证实，在iCCA中高表达的MT1X基因驱动肿瘤增殖、迁移和侵袭。结论：本研究建立了基于5个关键基因的TME预后模型，并阐明了它们在免疫抑制性TME中的作用。MT1X被证实是一种促肿瘤因子，突出了其作为治疗靶点的潜力。

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引用次数: 0

Advances in FLASH radiation therapy: A review on biological foundations and clinical prospects FLASH放射治疗的生物学基础和临床前景综述

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2026-03-01 Epub Date: 2026-01-16 DOI: 10.1016/j.tranon.2026.102676

Yupeng Di , Lingling Meng , Yingjie Wang , Jing Li

This paper provides a comprehensive review of the fundamental theories, clinical practices, technological advancements, current status, and future prospects of FLASH radiation therapy (FLASH-RT). As an emerging technique, FLASH-RT offers the potential to enhance therapeutic efficacy while minimizing damage to healthy tissues. We elaborate on the physical principles of the “FLASH effect” in radiation biology and its dose-distribution characteristics, describe clinical applications in tumor treatment, and evaluate protective effects on normal tissues. Furthermore, the review discusses technical advancements in equipment, dosimetry, and imaging, while analyzing current research hotspots and technical bottlenecks. We also examine pathological mechanisms, future applications, and prevailing controversies regarding safety, efficacy uncertainty, and ethics. This comprehensive discussion provides a valuable reference for deepening the understanding of FLASH-RT’s translational journey.

本文就FLASH放射治疗（FLASH- rt）的基本理论、临床实践、技术进展、现状及未来展望等方面进行了综述。作为一种新兴技术，FLASH-RT提供了提高治疗效果的潜力，同时最大限度地减少对健康组织的损害。我们阐述了辐射生物学中“FLASH效应”的物理原理及其剂量分布特征，描述了在肿瘤治疗中的临床应用，并评估了对正常组织的保护作用。此外，本文还讨论了设备、剂量学和成像方面的技术进展，同时分析了当前的研究热点和技术瓶颈。我们还研究了病理机制，未来的应用，以及关于安全性，疗效不确定性和伦理的普遍争议。这一全面的讨论为加深对FLASH-RT的转化之旅的理解提供了有价值的参考。

引用次数: 0

NEIL1 suppresses ROS accumulation to promote temozolomide resistance and malignant progression in glioma cells NEIL1抑制ROS积累，促进替莫唑胺耐药和胶质瘤细胞恶性进展

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2026-03-01 Epub Date: 2026-01-13 DOI: 10.1016/j.tranon.2026.102667

Shuo Li , Chenhao Fang , Qingyue Yuan , Xianzhen Chen

Background

Glioma is the most common malignant primary brain tumor. Temozolomide (TMZ) is the standard first-line chemotherapy, but its efficacy is severely limited by acquired resistance. Understanding resistance mechanisms, especially beyond traditional DNA repair, is crucial for improving outcomes.

Methods

We integrated multi-database glioma transcriptomics (TCGA, GTEx, CGGA). Bioinformatics (differential expression, WGCNA, glycolipid metabolism gene screening) and machine learning (LASSO, random forest) identified key genes, focusing on the DNA glycosylase NEIL1. Its expression was assessed in U251 MG cells versus TMZ-resistant (U251 MG/TMZ) cells. Gain/loss-of-function studies (lentiviral knockdown/overexpression) and pharmacological inhibition (a 2-thioxanthine derivative, TX16) were used to evaluate NEIL1′s role in proliferation (CCK-8, EdU), migration, invasion, apoptosis (TUNEL), ROS, and TMZ sensitivity (IC50). A subcutaneous nude mouse model provided in vivo validation.

Results

NEIL1 was aberrantly expressed in glioma and enriched in PI3K-Akt/cAMP signaling, suggesting that it may promote the malignant behavior of U251 MG cells through these pathways. Its expression was significantly higher in TMZ-resistant cells (P < 0.001). NEIL1 overexpression promoted malignant phenotypes (proliferation, migration, invasion, P < 0.05), while its knockdown suppressed them. Critically, NEIL1 overexpression attenuated TMZ-induced ROS and DNA damage, increased cell viability and IC₅₀ (1.2-fold), and bolstered TMZ resistance. The NEIL1 inhibitor TX16 reversed these malignant behaviors and restored TMZ sensitivity (P < 0.05), reinstating ROS-driven apoptosis. In vivo, NEIL1 promoted tumor growth, which was suppressed by TX16.

Conclusion

NEIL1 drives glioma malignancy and TMZ resistance by mitigating oxidative stress and DNA damage, highlighting its role as a promising target to overcome chemoresistance.

神经胶质瘤是最常见的原发性恶性脑肿瘤。替莫唑胺（TMZ）是标准的一线化疗药物，但其疗效受到获得性耐药的严重限制。了解耐药性机制，尤其是传统DNA修复机制之外的机制，对于改善治疗效果至关重要。方法整合多数据库胶质瘤转录组学（TCGA, GTEx， CGGA）。生物信息学（差异表达，WGCNA，糖脂代谢基因筛选）和机器学习（LASSO，随机森林）鉴定了关键基因，重点是DNA糖基化酶NEIL1。比较其在U251 MG细胞和TMZ耐药（U251 MG/TMZ）细胞中的表达。通过获得/丧失功能研究（慢病毒敲除/过表达）和药理学抑制（2-硫黄嘌呤衍生物TX16）来评估NEIL1在增殖（CCK-8, EdU）、迁移、侵袭、凋亡（TUNEL）、ROS和TMZ敏感性（IC50）中的作用。皮下裸鼠模型提供了体内验证。结果neil1在胶质瘤中异常表达，并在PI3K-Akt/cAMP信号通路中富集，提示其可能通过这些通路促进U251 MG细胞的恶性行为。其在tmz耐药细胞中的表达显著升高（P < 0.001）。NEIL1过表达促进恶性表型（增殖、迁移、侵袭，P < 0.05），而其敲低抑制这些表型。重要的是，NEIL1过表达减弱了TMZ诱导的ROS和DNA损伤，增加了细胞活力和IC50（1.2倍），并增强了TMZ抗性。NEIL1抑制剂TX16逆转了这些恶性行为，恢复了TMZ敏感性（P < 0.05），恢复了ros驱动的细胞凋亡。在体内，NEIL1促进肿瘤生长，而TX16抑制NEIL1的生长。结论neil1通过减轻氧化应激和DNA损伤驱动胶质瘤恶性和TMZ耐药，是克服化疗耐药的有希望的靶点。

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引用次数: 0

AlphaMissense pathogenicity scores predict response to immunotherapy and enhances the predictive capability of tumor mutation burden AlphaMissense致病性评分预测对免疫治疗的反应，增强肿瘤突变负荷的预测能力。

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2026-03-01 Epub Date: 2026-02-03 DOI: 10.1016/j.tranon.2026.102697

David Adeleke , Adewale Oluwaseun Fadaka , Nicole Remaliah Samantha Sibuyi , Ashwil Klein , Mervin Meyer , Gomes Rahul , Rick Jansen

Tumor Mutational Burden (TMB) is a widely used biomarker for selecting cancer patients for immune checkpoint inhibitor (ICI) therapy. However, TMB alone has limited predictive power, as it fails to account for the functional impact of mutations. We introduce AlphaTMB, a composite biomarker that integrates the quantity of mutations (TMB) with the qualitative assessment of their pathogenicity using AlphaMissense, a deep learning model that predicts the deleteriousness of missense variants. Using a pan-cancer cohort of 1,662 patients from the MSK-IMPACT study who received ICI therapy, we computed three scores per patient: TMB, Alpha (sum of AlphaMissense scores), and AlphaTMB (product of TMB and Alpha). Patients were stratified using both cancer-specific and pan-cancer quantiles. Survival outcomes were evaluated using Kaplan-Meier and multivariate Cox proportional hazards models, controlling for cancer type, age, and ICI regimen. AlphaTMB showed strong correlation with TMB (Spearman ρ = 0.866, p < 0.001), but offered improved prognostic accuracy. Patients in the bottom 80% AlphaTMB group had significantly poorer survival than those in the top 10% (HR < 2.51, p < 0.001), outperforming TMB and Alpha alone. AlphaTMB reclassified borderline cases, identifying subsets with low TMB but high deleterious mutation load, and vice versa. Gene mutation heatmaps and co-occurrence analysis confirmed that to 10% AlphaTMB-high tumors were enriched in mismatch repair and POLE mutations, reflecting a neoantigen-rich, immunotherapy-responsive phenotype. AlphaTMB improves survival prediction beyond TMB alone, better captures immunogenic tumor profiles, and reflects more accurate patient stratification. This AI derived somatic mutations pathogenicity scoring represents a step toward personalized immuno-oncology and merits further validation in prospective studies.

肿瘤突变负荷（Tumor Mutational Burden， TMB）是一种广泛使用的生物标志物，用于选择接受免疫检查点抑制剂（ICI）治疗的癌症患者。然而，TMB本身的预测能力有限，因为它无法解释突变对功能的影响。我们介绍了一种复合生物标志物alphaatmb，它将突变数量（TMB）与使用AlphaMissense（一种预测错义变异危害性的深度学习模型）对其致病性进行定性评估相结合。使用来自MSK-IMPACT研究的1,662例接受ICI治疗的泛癌症队列，我们计算了每位患者的三个评分：TMB， Alpha （AlphaMissense评分之和）和alphaatmb （TMB和Alpha的乘积）。采用癌症特异性分位数和泛癌症分位数对患者进行分层。使用Kaplan-Meier和多变量Cox比例风险模型评估生存结果，控制癌症类型、年龄和ICI方案。alphaatmb与TMB有很强的相关性（Spearman ρ = 0.866, p < 0.001），但可提高预后准确性。后80%的AlphaTMB组患者的生存率明显低于前10%的患者（HR < 2.51, p < 0.001），优于TMB和Alpha单独治疗。alphaatmb重新分类了临界病例，确定了低TMB但高有害突变负荷的亚群，反之亦然。基因突变热图和共现分析证实，高达10%的高alphatmb肿瘤富含错配修复和POLE突变，反映了一种富含新抗原、免疫治疗应答的表型。与单独的TMB相比，alphaatmb提高了生存预测，更好地捕获免疫原性肿瘤特征，并反映更准确的患者分层。这种人工智能衍生的体细胞突变致病性评分代表了个性化免疫肿瘤学的一步，值得在前瞻性研究中进一步验证。

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引用次数: 0

Computed tomography- and magnetic resonance imaging-based multi-modality radiomics models for predicting survival in esophageal cancer patients 基于计算机断层扫描和磁共振成像的多模态放射组学模型预测食管癌患者的生存。

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2026-03-01 Epub Date: 2026-02-05 DOI: 10.1016/j.tranon.2026.102686

Funing Chu , Dexuan Li , Zhaoqi Wang , Bingmei Bai , Keke Zhao , Shuting Wang , Chenglong Wang , Guang Yang , Jinrong Qu

Objectives

This study explores the integration of radiomics features from contrast-enhanced CT and MRI with clinical and radiological risk factors for optimal prognosis models of disease-free survival (DFS) and overall survival (OS) in esophageal squamous cell carcinoma (ESCC).

Materials and Methods

A retrospective study is undertaken of 371 ESCC patients who underwent contrast-enhanced CT and MRI with StarVIBE sequence, from September 2014 to December 2019. Prognosis models for DFS and OS were developed using cross-validation and Elastic-Net-Cox regression. Patients were grouped by treatment type (surgery, chemoradiotherapy, neoadjuvant therapy) to create single-modality and multi-modality models (Model-S, Model-CRT, and Model-nT). Model performance was evaluated using nomograms, calibration curves, and decision curves.

Results

Twelve optimal prognosis models were identified. For DFS, MRI c-indices were 0.595, 0.608, and 0.721, while CT c-indices were 0.686, 0.616, and 0.667. For OS, MRI c-indices were 0.692, 0.597, and 0.650, and CT c-indices were 0.656, 0.623, and 0.695. Multi-modality models demonstrated c-indices of 0.750, 0.695, 0.839 for DFS and 0.898, 0.777, 0.819 for OS.

Conclusion

Single-modality radiomics models exhibit limited predictive ability for DFS and OS in ESCC patients, whereas multi-modality radiomics models enhance predictive accuracy significantly.

目的：本研究将增强CT和MRI的放射组学特征与临床和放射学危险因素结合起来，探讨食管鳞状细胞癌（ESCC）无病生存期（DFS）和总生存期（OS）的最佳预后模型。材料与方法：对2014年9月至2019年12月接受StarVIBE序列增强CT和MRI扫描的371例ESCC患者进行回顾性研究。采用交叉验证和Elastic-Net-Cox回归建立DFS和OS的预后模型。根据治疗类型（手术、放化疗、新辅助治疗）对患者进行分组，建立单模式和多模式（Model-S、Model-CRT和Model-nT）。模型性能评估采用诺图，校准曲线和决策曲线。结果：确定了12种最佳预后模型。DFS MRI c-指数分别为0.595、0.608、0.721，CT c-指数分别为0.686、0.616、0.667。OS组MRI c指数分别为0.692、0.597、0.650，CT c指数分别为0.656、0.623、0.695。多模态模型显示，DFS的c指数分别为0.750、0.695、0.839，OS的c指数分别为0.898、0.777、0.819。结论：单模态放射组学模型对ESCC患者DFS和OS的预测能力有限，而多模态放射组学模型可显著提高预测准确性。

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引用次数: 0

RHOJ-induced chemotherapy resistance through epithelial–mesenchymal transition in drug-tolerant persister cells of head and neck cancer rhoj通过上皮-间质转化诱导头颈癌耐药持久细胞的化疗耐药

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2026-03-01 Epub Date: 2026-01-17 DOI: 10.1016/j.tranon.2026.102673

Hang Huong Ling , Chih-Ming Huang , Ming-Shou Hsieh , Vijesh Kumar Yadav , Iat-Hang Fong , Kuang-Tai Kuo , Chi-Tai Yeh , Jo-Ting Tsai

Background: Building on our previous identification of TXNRD1 and RHOJ as mediators of immunotherapy resistance in head and neck squamous cell carcinoma (HNSCC), this study investigates the role of RHOJ in regulating endothelial markers and signaling pathways in drug-tolerant persister (DTP) cells, as well as its contribution to immune suppression within the resistant tumor microenvironment. Methods: We examined the role of RHOJ in regulating tumor-associated macrophage polarization and enhancing M1 antitumor activity and evaluated the therapeutic potential of targeting the RHOJ/Rho kinase axis in an HNSCC DTP mouse model. Results: RHOJ expression was significantly upregulated in HNSCC DTP cells. RHOJ contributes to chemoresistance by increasing oxidative stress and initiating the DNA damage response. RNA sequencing revealed that the IPO9/EpCAM signaling pathway positively regulates RHOJ expression. Knockdown of RHOJ with shRNA suppressed HNSCC DTP cell migration and downregulated IPO9/EpCAM signaling. Gene enrichment analysis revealed high RHOJ expression in tumor-associated endothelial cells. Treatment with the RHOJ-dependent F-actin inhibitor Latrunculin B (HY-101,848) impaired actin polymerization and increased the chemosensitivity of HNSCC DTP cells. Silencing RHOJ inhibited M2 tumor-associated macrophage activation. RHOJ overexpression promoted M2 macrophage proliferation. Conclusion: RHOJ plays a critical role in modulating immunosuppressive signaling in both tumor and endothelial cells. RHOJ promotes the function of tumor-associated endothelial cells and drives EMT through its interaction with the IPO9/EpCAM signaling pathway, thereby increasing cell survival and drug resistance. Additionally, RHOJ may limit immune cell infiltration into the tumor core and promote immune evasion by contributing to vascular abnormalities and impaired barrier function.

背景：在我们之前确定TXNRD1和RHOJ是头颈部鳞状细胞癌（HNSCC）免疫治疗耐药的介质的基础上，本研究探讨了RHOJ在调节耐药持续性（DTP）细胞内皮标志物和信号通路中的作用，以及它在耐药肿瘤微环境中的免疫抑制作用。方法：研究RHOJ在调节肿瘤相关巨噬细胞极化和增强M1抗肿瘤活性中的作用，并在HNSCC DTP小鼠模型中评估靶向RHOJ/Rho激酶轴的治疗潜力。结果：RHOJ在HNSCC DTP细胞中表达显著上调。RHOJ通过增加氧化应激和启动DNA损伤反应来促进化学耐药。RNA测序结果显示，ip9 /EpCAM信号通路正调控RHOJ的表达。shRNA敲低RHOJ抑制HNSCC DTP细胞迁移，下调ip9 /EpCAM信号。基因富集分析显示RHOJ在肿瘤相关内皮细胞中高表达。rhoj依赖性f -肌动蛋白抑制剂Latrunculin B （hy - 101848）抑制了肌动蛋白聚合，增加了HNSCC DTP细胞的化学敏感性。沉默RHOJ抑制M2肿瘤相关巨噬细胞活化。RHOJ过表达促进M2巨噬细胞增殖。结论：RHOJ在肿瘤和内皮细胞免疫抑制信号的调节中起关键作用。RHOJ通过与ip9 /EpCAM信号通路的相互作用，促进肿瘤相关内皮细胞的功能，驱动EMT，从而提高细胞存活率和耐药能力。此外，RHOJ可能通过导致血管异常和屏障功能受损来限制免疫细胞浸润到肿瘤核心并促进免疫逃避。

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