EMP1与α-SMA在乳腺癌中的表达及其对肿瘤微环境和预后的影响  

Expressions of EMP1 andα-SMA in Breast Cancer and Their Impact on Tumor Microenvironment and Prognosis

作　　者：王琪 杨楠[3] 陈静 田林 李凯 苏占海 杨建业[5] WANG Qi;YANG Nan;CHEN Jing;TIAN Lin;LI Kai;SU Zhan-hai;YANG Jian-ye(Department of Pathology,Renmin Hospital,Hubei University of Medicine,Shiyan,Hubei 442000;Qinghai Plateau Medicine Laboratory,College of Medicine,Qinghai University,Xining,Qinghai 810001;Department of Endocrinology,Renmin Hospital,Hubei University of Medicine;Department of Traditional Chinese Medicine and Acupuncture,Renmin Hospital,Hubei University of Medicine;Research Institute of Clinical Medicine,Renmin Hospital,Hubei University of Medicine,Shiyan,Hubei 442000,China)

机构地区：[1]湖北医药学院附属人民医院病理科,湖北十堰442000 [2]青海大学医学院青海省高原医学实验室,青海西宁810001 [3]湖北医药学院附属人民医院内分泌科 [4]湖北医药学院附属人民医院中医针灸科 [5]湖北医药学院附属人民医院临床医学研究所,湖北十堰442000

出　　处：《湖北医药学院学报》2025年第2期126-131,143,F0002,共8页Journal of Hubei University of Medicine

基　　金：国家自然科学基金(82274155、32360242);湖北省自然科学基金联合项目(2025AFD200);十堰市引导性科研项目(24Y085)。

摘　　要：目的:探讨上皮膜蛋白1(EMP1)和α平滑肌肌动蛋白(α-SMA)在激素敏感型乳腺癌中的表达变化及其对患者预后的影响,进一步揭示其在肿瘤微环境中的作用机制。方法:选取60例乳腺癌患者的肿瘤组织及癌旁正常组织,采用免疫组化(IHC)、实时定量PCR(RT-qPCR)技术检测EMP1和α-SMA的表达水平。建立MCF7细胞与癌症相关成纤维细胞(CAF)的共培养模型,模拟肿瘤微环境,用Western Blot和Transwell等技术评估CAF对乳腺癌细胞迁移和侵袭能力的影响。通过Kaplan-Meier生存曲线和Cox比例风险回归分析,评估EMP1和α-SMA的表达与患者预后的相关性。结果:免疫组化和RT-PCR结果显示,乳腺癌组织中α-SMA的表达显著上调,而EMP1的表达显著下调(P<0.05)。Western Blot和Transwell实验结果表明,CAF共培养体系显著增强了乳腺癌细胞的迁移和侵袭能力(P<0.05)。生存分析显示,α-SMA高表达和EMP1低表达的患者预后较差(P<0.05),二者的表达呈负相关(R=0.5,P<0.05)。结论:EMP1的低表达与乳腺癌的高侵袭性和较差预后密切相关,而α-SMA的高表达则促进了CAF的活化和肿瘤进展。EMP1与α-SMA的相互作用在乳腺癌微环境中发挥重要作用,提示联合靶向这两种蛋白可能为乳腺癌的治疗提供新策略。Objective To investigate the changes of epithelial membrane protein 1(EMP1)andα-smooth muscle actin(α-SMA)in hormone-sensitive breast cancer and their effects on patients′prognosis,and to further reveal their mechanisms in the tumor microenvironment.Methods Tumor tissues and adjacent normal tissues from 60 breast cancer patients were se⁃lected.The expressions of EMP1 andα-SMA were detected using immunohistochemistry(IHC),real-time quantitative PCR(RT-qPCR),and Western blot.A co-culture model of MCF7 cells and cancer-associated fibroblasts(CAFs)was established to simulate the tumor microenvironment and assess the effect of CAFs on the migration and invasion of breast cancer cells.The correlation between EMP1 andα-SMA and patients′prognosis was assessed by Kaplan-Meier curves and Cox proportional hazards model.Results Immunohistochemistry and RT-qPCR revealed thatα-SMA was up-regulated in breast cancer tissues,whereas EMP1 was down-regulated(P<0.05).Western blot and scratch wound assay demonstrated that the CAF co-culture system enhanced the migration and invasion of breast cancer cells(P<0.05).The survival analysis indicated that patients with increasedα-SMA and decreased EMP1 had a poor prognosis(P<0.05),and their expressions were negatively correlated(R=0.5,P<0.05).Conclusion Low EMP1 is closely associated with high invasiveness and poor prognosis in breast cancer,while highα-SMA promotes CAF activation and tumor progression.The interaction between EMP1 andα-SMA plays an important role in the tumor microenvironment,suggesting that joint targeting of these two pro⁃teins may provide a new strategy for the treatment of breast cancer.

关 键 词：EMP1 Α-SMA 乳腺癌 肿瘤微环境 CAF EMT 

分 类 号：R737.9[医药卫生—肿瘤]