7-甲基鸟苷（m7G）甲基化METTL1是透明细胞肾细胞癌进展的潜在生物标志物。

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2024-11-20 DOI:10.1016/j.tranon.2024.102202

Yi Liu , Yanji Zhan , Jiao Liu , Zhengze Shen , Yudong Hu , Ling Zhong , Yuan Yu , Bin Tang , Jing Guo

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引用次数: 0

摘要

背景：透明细胞肾细胞癌（ccRCC）是最常见的肾癌亚型。据报道，7-甲基鸟苷（m7G）是最常见的 RNA 修饰之一，在 ccRCC 的进展中发挥着重要作用；然而，参与这一功能的特定 m7G 修饰调节因子仍不清楚。本研究旨在利用无监督机器学习方法探讨m7G甲基化调节因子与ccRCC进展之间的相关性：方法：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，找出与ccRCC患者总生存期相关的m7G相关差异表达基因。为了构建和验证预后风险模型，TCGA 数据集样本被分为训练集和测试集。利用最小绝对缩减和选择算子Cox回归分析构建了多基因风险特征，并利用Cox回归和生存分析评估了其预后意义。最后，进行免疫组化以验证该特征的预后意义：本研究共纳入了 537 例 ccRCC 患者。我们发现有 26 个 m7G RNA 甲基化调节因子有显著的差异表达。单变量和多因素 Cox 回归分析显示，METTL1 的表达与 ccRCC 的进展相关：结论：与 m7G 相关的 METTL1 可作为 ccRCC 预后和诊断的潜在生物标志物。结论：与 m7G 相关的 METTL1 可作为 ccRCC 预后和诊断的潜在生物标志物，此外，它还可能通过调节肿瘤免疫微环境影响 ccRCC 的预后，为免疫疗法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一个新的视角。

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The 7-Methylguanosine (m7G) methylation METTL1 acts as a potential biomarker of clear cell renal cell carcinoma progression

Background: 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.

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.

Results: 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.

Conclusions: 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.

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.