Lu Xiaoqin, Ying Yanqi, Zhang Wenyi, Li Rui, Zhang Jingyan
Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
Cell Biol Int. 2023 Jan;47(1):201-215. doi: 10.1002/cbin.11925. Epub 2022 Oct 8.
Several studies have shown that MutS homolog 2 (MSH2) is highly expressed in many cancer tissues. Transcriptome expression data were collected from the Cancer Genome Atlas (TCGA) database. We analyzed the expression of MSH2 in normal and tumor tissues, the relationship between MSH2 expression and various prognostic factors, and the relationship between MSH2 expression and overall survival, disease specific survival, and progression free interval. We also examined MSH2 promoter methylation between endometrial cancer and normal endometrial tissues, and identified the prognostic value of MSH2 methylation in endometrial cancer. MSH2 was highly expressed in endometrial cancer tumor tissues compared with normal tissues. High MSH2 expression might be an independent prognostic factor for OS, DSS, and PFI. Further, high MSH2 expression was correlated with age and histological type, but not with BMI, clinical stage, tumor invasion, or other clinical features. MSH2 promoter methylation in endometrial cancer was significantly lower than in normal tissues. Additionally, MSH2 levels, OS, DSS, and PFI were associated with BMI, age, tumor invasion, and histological type. ssGSEA showed that MSH2 expression was positively correlated with the infiltration of Th2 cells, Tcm cells, T helper cells, and Tgd cells, whereas it was negatively correlated with NK CD56 bright cells, pDC cells, iDC cells, cytotoxic cells, and neutrophils. Increased MSH2 expression and reduced MSH2 methylation in endometrial cancer predicts poor prognosis. MSH2 may be used as a biomarker for the diagnosis and prognosis of endometrial cancer and as an immunotherapy target.
多项研究表明,错配修复蛋白同源物2(MSH2)在许多癌症组织中高表达。从癌症基因组图谱(TCGA)数据库收集转录组表达数据。我们分析了MSH2在正常组织和肿瘤组织中的表达、MSH2表达与各种预后因素之间的关系,以及MSH2表达与总生存期、疾病特异性生存期和无进展生存期之间的关系。我们还检测了子宫内膜癌组织与正常子宫内膜组织之间MSH2启动子甲基化情况,并确定了MSH2甲基化在子宫内膜癌中的预后价值。与正常组织相比,MSH2在子宫内膜癌肿瘤组织中高表达。高MSH2表达可能是总生存期、疾病特异性生存期和无进展生存期的独立预后因素。此外,高MSH2表达与年龄和组织学类型相关,但与体重指数、临床分期、肿瘤浸润或其他临床特征无关。子宫内膜癌中MSH2启动子甲基化明显低于正常组织。此外,MSH2水平、总生存期、疾病特异性生存期和无进展生存期与体重指数、年龄、肿瘤浸润和组织学类型有关。单样本基因集富集分析(ssGSEA)显示,MSH2表达与Th2细胞、中央记忆T细胞(Tcm细胞)、辅助性T细胞和γδT细胞(Tgd细胞)的浸润呈正相关,而与自然杀伤CD56bright细胞、浆细胞样树突状细胞(pDC细胞)、髓样树突状细胞(iDC细胞)、细胞毒性细胞和中性粒细胞呈负相关。子宫内膜癌中MSH2表达增加和MSH2甲基化减少预示预后不良。MSH2可作为子宫内膜癌诊断和预后的生物标志物以及免疫治疗靶点。