Liu Yi, Zhan Yanji, Liu Jiao, Shen Zhengze, Hu Yudong, Zhong Ling, Yu Yuan, Tang Bin, Guo Jing
Department of Nephrology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China; The 3rd Affiliated Hospital, Chengdu Medical College, Chengdu Pidu District People's Hospital, Chengdu, 611730, China.
Department of Nephrology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
Transl Oncol. 2025 Jan;51:102202. doi: 10.1016/j.tranon.2024.102202. Epub 2024 Nov 20.
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer. 7-Methylguanosine (m7G), one of the most prevalent RNA modifications, has been reported to play an important role in ccRCC progression; however, the specific regulators of m7G modification that are involved in this function remain unclear. This study aimed to explore the correlation between regulators of m7G methylation and ccRCC progression using unsupervised machine learning methods.
Transcriptome and clinical data of ccRCC were retrieved from The Cancer Genome Atlas (TCGA) database to identify differentially expressed m7G-related genes associated with the overall survival of patients with ccRCC. To construct and validate a prognostic risk model, TCGA dataset samples were divided into training and test sets. A multiple-gene risk signature was constructed using least absolute shrinkage and selection operator Cox regression analysis, and its prognostic significance was assessed using Cox regression and survival analyses. Finally, immunohistochemistry was performed to verify the prognostic significance of this signature.
In total, 537 patients with ccRCC were included in this study. We found that 26 m7G RNA methylation regulators that were significantly differentially expressed. Univariate and multifactorial Cox regression analyses revealed that METTL1 expression was associated with ccRCC progression.
METTL1 associated with m7G may serve as a potential biomarker for ccRCC prognosis and diagnosis. Moreover, it may affect the prognosis of ccRCC by regulating the tumor immune microenvironment, providing a potential therapeutic target for immunotherapy. These results provide a new perspective on the role of M7G-related RNAs in ccRCC pathogenesis.
透明细胞肾细胞癌（ccRCC）是肾癌最常见的亚型。7-甲基鸟苷（m7G）是最普遍的RNA修饰之一，据报道在ccRCC进展中起重要作用；然而，参与此功能的m7G修饰的具体调节因子仍不清楚。本研究旨在使用无监督机器学习方法探索m7G甲基化调节因子与ccRCC进展之间的相关性。
从癌症基因组图谱（TCGA）数据库中检索ccRCC的转录组和临床数据，以鉴定与ccRCC患者总生存期相关的差异表达的m7G相关基因。为构建和验证预后风险模型，将TCGA数据集样本分为训练集和测试集。使用最小绝对收缩和选择算子Cox回归分析构建多基因风险特征，并使用Cox回归和生存分析评估其预后意义。最后，进行免疫组织化学以验证该特征的预后意义。
本研究共纳入537例ccRCC患者。我们发现26个m7G RNA甲基化调节因子有显著差异表达。单因素和多因素Cox回归分析显示，METTL1表达与ccRCC进展相关。
与m7G相关的METTL1可能作为ccRCC预后和诊断的潜在生物标志物。此外，它可能通过调节肿瘤免疫微环境影响ccRCC的预后，为免疫治疗提供潜在的治疗靶点。这些结果为M7G相关RNA在ccRCC发病机制中的作用提供了新的视角。
