5-Methylcytosine (m5C) Modification Patterns and Tumor Immune Infiltration Characteristics in Clear Cell Renal Cell Carcinoma

Abstract

Recently, studies have revealed the prognostic value of 5-methylcytosine (m5C) in clear cell renal cell carcinoma (ccRCC). However, the role of m5C methylation in ccRCC immune infiltration and the immunotherapeutic response remains unknown. Based on the mRNA expressions of 14 m5C regulators, we evaluated the m5C modification patterns of 530 tumor samples from the TCGA-ccRCC database. We used the principal component analysis (PCA) algorithm to construct individual patient m5Cscores to facilitate individual analysis of m5C modification patterns in ccRCC patients. We finally defined three different m5C modification patterns. Different clinical features and immune heterogeneity existed among the three patterns, and their immune infiltration characteristics could correspond to different immune phenotypes, including the immune-inflamed, immune-excluded, and immune-desert phenotype. We designed the m5Cscore calculated by the PCA algorithm to measure individual patients’ m5C modification patterns. The low m5Cscore group presented with a positive prognosis, increased TMB, and immune activation. Additionally, low m5Cscore patients showed an increased response to immune checkpoint inhibitors. We further the value of the m5Cscore in predicting OS verified in four other tumor cohorts. Our findings revealed that m5C methylation modifications are essential in regulating ccRCC immune infiltration. Assessing single ccRCC patients’ m5C modification patterns can fully improve our comprehension of tumor immune characteristics and be used to provide effective personalized immunotherapy strategies for clinical use.

Keywords

• ccRCC
• TCGA
• m5C methylation
• tumor immune microenvironment
• immunotherapy