ITM2A as a potential prognostic marker for triple-negative breast cancer.

IF 3.3 3区 医学 Q2 ONCOLOGY
Journal of Cancer Pub Date : 2025-06-23 eCollection Date: 2025-01-01 DOI:10.7150/jca.114801
Can Jiang, Ruixin Feng, Yongqian Zhao, Jingting Zhang, Na Han, Yuzhu Zhang, Guang Shu, Gang Yin, Maonan Wang
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引用次数: 0

Abstract

Different subtypes of breast cancer pose great challenges for precision therapy, especially triple-negative breast cancer (TNBC), because it lacks effective therapeutic targets and is highly resistant to chemotherapy. In this study, the transmembrane protein ITM2A was systematically identified as a novel prognostic biomarker and potential therapeutic target for TNBC. ITM2A was found to be significantly under expressed in TNBC tissues, as revealed by differential expression profiling. Furthermore, patients exhibiting low ITM2A expression demonstrated worse overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS). A combined multi-omics analysis revealed a significant association between low ITM2A expression and immunosuppressive microenvironmental features. It is noteworthy that the ITM2A high-expression group exhibited substantial clinical benefits in anti-PD-L1 treatment (AUC=0.982) and CAR-T treatment (AUC=0.827). Gene Ontology functional annotation and KEGG pathway enrichment analysis indicated that ITM2A may coordinate anti-tumor immune responses by regulating copper ion metabolic reprogramming and immune checkpoint networks. Pharmacogenomic analysis further confirmed that the expression level of ITM2A was negatively correlated with the sensitivity of etoposide. By establishing the 'immunometabolism-therapeutic response' regulatory axis of ITM2A, this study hopes to provide an innovative theoretical basis for the targeted treatment of TNBC and the precise stratification of immunotherapy.

ITM2A作为三阴性乳腺癌的潜在预后标志物
不同亚型的乳腺癌,尤其是三阴性乳腺癌(TNBC),由于缺乏有效的治疗靶点和对化疗的高度耐药,给精准治疗带来了很大的挑战。在这项研究中,跨膜蛋白ITM2A被系统地鉴定为一种新的预后生物标志物和潜在的TNBC治疗靶点。通过差异表达谱分析发现,ITM2A在TNBC组织中明显表达不足。此外,ITM2A低表达的患者表现出更差的总生存期(OS)、无复发生存期(RFS)和远端无转移生存期(DMFS)。一项联合多组学分析显示,低ITM2A表达与免疫抑制微环境特征之间存在显著关联。值得注意的是,ITM2A高表达组在抗pd - l1治疗(AUC=0.982)和CAR-T治疗(AUC=0.827)中均表现出可观的临床获益。基因本体功能注释和KEGG通路富集分析表明,ITM2A可能通过调节铜离子代谢重编程和免疫检查点网络来协调抗肿瘤免疫应答。药物基因组学分析进一步证实ITM2A的表达水平与依托波苷的敏感性呈负相关。本研究希望通过建立ITM2A的“免疫代谢-治疗反应”调控轴,为TNBC的靶向治疗和免疫治疗的精准分层提供创新的理论依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Cancer
Journal of Cancer ONCOLOGY-
CiteScore
8.10
自引率
2.60%
发文量
333
审稿时长
12 weeks
期刊介绍: Journal of Cancer is an open access, peer-reviewed journal with broad scope covering all areas of cancer research, especially novel concepts, new methods, new regimens, new therapeutic agents, and alternative approaches for early detection and intervention of cancer. The Journal is supported by an international editorial board consisting of a distinguished team of cancer researchers. Journal of Cancer aims at rapid publication of high quality results in cancer research while maintaining rigorous peer-review process.
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