VTCN1导致HR+乳腺癌预后不良及内分泌治疗耐药  

VTCN1 causes poor prognosis and endocrine therapy resistance in HR+breast cancer

作　　者：宋雅雯 郭联涛 孔德光 孙圣荣[1] SONG Yawen;GUO Liantao;KONG Deguang;SUN Shengrong(Department of Breast and Thyroid Surgery,Renmin Hospital of Wuhan University,Wuhan 430060,Hubei,China)

机构地区：[1]武汉大学人民医院乳腺甲状腺外科,湖北武汉430060

出　　处：《山东大学学报(医学版)》2025年第1期43-59,共17页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(82103671)。

摘　　要：目的探讨激素受体阳性(特别是Luminal A型)乳腺癌内分泌治疗耐药的相关机制,以克服其临床治疗挑战并改善患者预后。方法本研究运用生物信息学技术,筛选出内分泌治疗敏感与耐药患者间差异表达的基因。通过泛癌分析、Kaplan-Meier生存分析、蛋白质互作网络构建、肿瘤免疫浸润细胞相关性分析以及体外细胞实验,推测验证目标基因发挥作用的可能机制。结果VTCN1能减弱他莫昔芬在MCF7和T47D细胞中的抗癌效果。该基因可能通过Notch4、Slug、Sox2、LAG3、PD-L1等调节因子改变肿瘤微环境,尤其是肿瘤免疫微环境,促进上皮间质转化(epithelial-mesenchymal transition,EMT),并影响激素受体表达,最终导致他莫昔芬耐药。结论VTCN1通过EMT相关因子调控肿瘤微环境,进而导致激素受体阳性乳腺癌对内分泌治疗耐药。Objective To investigate the mechanisms associated with endocrine therapy resistance in hormone receptorpositive(particularly Luminal A subtype)breast cancer,for overcoming clinical treatment challenges and improving patient outcomes.Methods Bioinformatics techniques were used to identify differential expression genes between endocrine therapy-sensitive and drug-resistant patients.Through pan-cancer analysis,Kaplan-Meier survival analysis,protein interaction network construction,correlation analysis with tumor-infiltrating immune cells,and in vitro cell experiments,the potential mechanisms underlying the role of the target gene were speculated and validated.Results VTCN1 attenuated the anticancer effect of Tamoxifen in MCF7 and T47D cells.This gene might alter the tumor microenvironment,particularly the tumor immune microenvironment,through regulatory factors such as Notch4,Slug,Sox2,LAG3,and PD-L1,promote epithelial-mesenchymal transition(EMT)and affect hormone receptor expression,ultimately lead to Tamoxifen resistance.Conclusion VTCN1 regulates the tumor microenvironment through EMT-related factors,thereby contributing to endocrine therapy resistance in hormone receptor-positive breast cancer.

关 键 词：乳腺癌 VTCN1 内分泌治疗耐药 他莫昔芬 肿瘤微环境 激素受体 上皮间质转化 

分 类 号：R737.9[医药卫生—肿瘤]