Xu Jing, Cen Xiaoxia, Yao Yu, Zhao Suo, Li Wei, Zhang Wei, Qiu Ming
Department of General Surgery, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
J Oncol. 2022 Sep 26;2022:2735251. doi: 10.1155/2022/2735251. eCollection 2022.
Triple-negative breast cancer (TNBC) is a widely prevalent breast cancer, with a mortality rate of up to 25%. TNBC has a lower survival rate, and the significance of N7-methylguanosine (m7G) modification in TNBC remains unclear. Thus, this study is aimed at investigating m7G-related miRNAs in TNBC patients through in silico analysis. In our research, RNA sequencing and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. The miRNAs targeting typical m7G modification regulators Methyltransferase-like 1 (METTL1) and WD repeat domain 4 (WDR4) were predicted on the TargetScan website. A miRNA risk model was built, and its prognostic value was evaluated by R soft packages. Single-sample gene set enrichment analysis was used to assess immune infiltration, and further expression of immune checkpoints was investigated. As a result, miR-421, miR-5001-3p, miR-4326, miR-1915-3p, miR-3177-5p, and miR-4505 were identified to create the risk model. A nomogram consisting of the stage N and risk model predicted overall survival effectively among TNBC patients. Treg and TIL were shown to be strongly linked to the risk model, and the high-risk group had higher levels of four immune checkpoints expression (CD28, CTLA-4, ICOS, and TNFRSF9). A risk model consisting of m7G-related miRNAs was constructed. The findings of the current study could be used as a prognostic biomarker and can provide a novel immunotherapy insight for TNBC patients.
三阴性乳腺癌（TNBC）是一种广泛流行的乳腺癌，死亡率高达25%。TNBC的生存率较低，N7-甲基鸟苷（m7G）修饰在TNBC中的意义仍不清楚。因此，本研究旨在通过计算机分析调查TNBC患者中与m7G相关的微小RNA（miRNA）。在我们的研究中，RNA测序和临床数据来自癌症基因组图谱（TCGA）数据库。在TargetScan网站上预测了靶向典型m7G修饰调节因子甲基转移酶样1（METTL1）和WD重复结构域4（WDR4）的miRNA。构建了一个miRNA风险模型，并通过R软件包评估其预后价值。使用单样本基因集富集分析来评估免疫浸润，并进一步研究免疫检查点的表达。结果，鉴定出miR-421、miR-5001-3p、miR-4326、miR-1915-3p、miR-3177-5p和miR-4505以创建风险模型。由N分期和风险模型组成的列线图在TNBC患者中有效预测了总生存期。调节性T细胞（Treg）和肿瘤浸润淋巴细胞（TIL）被证明与风险模型密切相关，高危组的四种免疫检查点表达（CD28、细胞毒性T淋巴细胞相关蛋白4（CTLA-4）、诱导共刺激分子（ICOS）和肿瘤坏死因子受体超家族成员9（TNFRSF9））水平较高。构建了一个由与m7G相关的miRNA组成的风险模型。本研究结果可作为一种预后生物标志物，并可为TNBC患者提供新的免疫治疗见解。
