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鉴定和验证 mG 修饰模式,并对透明细胞肾细胞癌的肿瘤微环境浸润进行多组学分析。

Identification and Verification of mG Modification Patterns and Characterization of Tumor Microenvironment Infiltration Multi-Omics Analysis in Clear Cell Renal Cell Carcinoma.

机构信息

Department of Urology, Changhai Hospital, Naval Medical University, Shanghai, China.

Department of Urology, Changzheng Hospital, Naval Medical University, Shanghai, China.

出版信息

Front Immunol. 2022 May 3;13:874792. doi: 10.3389/fimmu.2022.874792. eCollection 2022.

Abstract

The epigenetic modification of tumorigenesis and progression in neoplasm has been demonstrated in recent studies. Nevertheless, the underlying association of N7-methylguanosine (mG) regulation with molecular heterogeneity and tumor microenvironment (TME) in clear cell renal cell carcinoma (ccRCC) remains unknown. We explored the expression profiles and genetic variation features of mG regulators and identified their correlations with patient outcomes in pan-cancer. Three distinct mG modification patterns, including MGCS1, MGCS2, and MGCS3, were further determined and systematically characterized multi-omics data in ccRCC. Compared with the other two subtypes, patients in MGCS3 exhibited a lower clinical stage/grade and better prognosis. MGCS1 showed the lowest enrichment of metabolic activities. MGCS2 was characterized by the suppression of immunity. We then established and validated a scoring tool named m7Sig, which could predict the prognosis of ccRCC patients. This study revealed that mG modification played a vital role in the formation of the tumor microenvironment in ccRCC. Evaluating the mG modification landscape helps us to raise awareness and strengthen the understanding of ccRCC's characterization and, furthermore, to guide future clinical decision making.

摘要

近年来的研究表明,肿瘤发生和进展存在表观遗传修饰。然而,在透明细胞肾细胞癌(ccRCC)中,N7-甲基鸟苷(mG)调控与分子异质性和肿瘤微环境(TME)的潜在关联尚不清楚。我们在泛癌中探索了 mG 调节因子的表达谱和遗传变异特征,并确定了它们与患者预后的相关性。进一步确定了三种不同的 mG 修饰模式,包括 MGCS1、MGCS2 和 MGCS3,并对 ccRCC 的多组学数据进行了系统表征。与其他两种亚型相比,MGCS3 亚型的患者具有较低的临床分期/分级和更好的预后。MGCS1 表现出最低的代谢活性富集。MGCS2 的特征是免疫抑制。我们随后建立并验证了一个名为 m7Sig 的评分工具,它可以预测 ccRCC 患者的预后。本研究揭示了 mG 修饰在 ccRCC 肿瘤微环境形成中发挥了重要作用。评估 mG 修饰图谱有助于提高我们对 ccRCC 特征的认识和理解,并进一步指导未来的临床决策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d9e/9113293/26338f2249ed/fimmu-13-874792-g001.jpg

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