Li Wenhao, Wang Xiaolong, Li Chen, Chen Tong, Zhou Xianyong, Li Zheng, Yang Qifeng
Department of Breast Surgery, General Surgery, Cheeloo College of Medicine, Qilu Hospital of Shandong University, Wenhua Xi Road No. 107, Jinan, 250012, Shandong, China.
Department of Breast Surgery, Binzhou People's Hospital, Binzhou, Shandong, China.
Hum Cell. 2023 Jan;36(1):393-408. doi: 10.1007/s13577-022-00826-x. Epub 2022 Nov 20.
Breast cancer is the most prevalent cancer, and it is accompanied by high heterogeneity. N6-methyladenosine (m6A) modification significantly contributes to breast cancer tumorigenesis and progression. However, how m6A-related genes affect the clinical outcomes and tumor immune microenvironment (TIME) of breast cancer is largely unknown. Our study developed an m6A-related gene signature on the basis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The m6A-related gene signature was constructed using univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Breast cancer patients were classified into low- and high-risk groups depending on the median risk score. The reliability and efficiency of the signature were validated using Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, and principal component analysis (PCA). The risk score was validated as an independent indicator associated with overall survival, and a nomogram model was created to estimate the overall survival of patients with breast cancer. Functional annotation suggested that the risk score had a strong relationship with immune-related pathways. Different proportions of immune cell infiltration between the two groups were evaluated using various algorithms. The high-risk group had higher immune checkpoint expression levels. We discovered that one of the 6 prognostic genes, TMEM71, was downregulated in breast cancer tissues. In vitro experiments indicated that overexpression of TMEM71 suppressed breast cancer cell proliferation and migration. In conclusion, the m6A-related gene signature may be a sensitive biomarker for overall survival prediction and guide the individualized treatment for breast cancer patients.
乳腺癌是最常见的癌症，且具有高度异质性。N6-甲基腺苷（m6A）修饰对乳腺癌的肿瘤发生和进展有显著影响。然而，m6A相关基因如何影响乳腺癌的临床结局和肿瘤免疫微环境（TIME）在很大程度上尚不清楚。我们的研究基于癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）开发了一种m6A相关基因特征。该m6A相关基因特征通过单变量、最小绝对收缩和选择算子（LASSO）以及多变量Cox回归分析构建。根据中位风险评分将乳腺癌患者分为低风险组和高风险组。使用Kaplan-Meier分析、受试者工作特征（ROC）曲线和主成分分析（PCA）验证了该特征的可靠性和有效性。风险评分被验证为与总生存期相关的独立指标，并创建了列线图模型来估计乳腺癌患者的总生存期。功能注释表明风险评分与免疫相关途径有密切关系。使用各种算法评估了两组之间不同比例的免疫细胞浸润情况。高风险组的免疫检查点表达水平较高。我们发现6个预后基因之一的跨膜蛋白71（TMEM71）在乳腺癌组织中表达下调。体外实验表明，TMEM71的过表达抑制了乳腺癌细胞的增殖和迁移。总之，m6A相关基因特征可能是预测总生存期的敏感生物标志物，并可为乳腺癌患者的个体化治疗提供指导。
