Characterization of the m6A-Associated Tumor Immune Microenvironment in Prostate Cancer to Aid Immunotherapy

Front Immunol. 2021 Aug 31:12:735170. doi: 10.3389/fimmu.2021.735170. eCollection 2021.

Abstract

The aim of this study was to elucidate the correlation between m6A modification and the tumor immune microenvironment (TIME) in prostate cancer (PCa) and to identify the m6A regulation patterns suitable for immune checkpoint inhibitors (ICIs) therapy. We evaluated the m6A regulation patterns of PCa based on 24 m6A regulators and correlated these modification patterns with TIME characteristics. Three distinct m6A regulation patterns were determined in PCa. The m6A regulators cluster with the best prognosis had significantly increased METTL14 and ZC3H13 expression and was characterized by low mutation rate, tumor heterogeneity, and neoantigens. The m6A regulators cluster with a poor prognosis had markedly high KIAA1429 and HNRNPA2B1 expression and was characterized by high intratumor heterogeneity and Th2 cell infiltration, while low Th17 cell infiltration and Macrophages M1/M2. The m6Ascore was constructed to quantify the m6A modification pattern of individual PCa patients based on m6A-associated genes. We found that the low-m6Ascore group with poor prognosis had a higher immunotherapeutic response rate than the high-m6Ascore group. The low-m6Ascore group was more likely to benefit from ICIs therapy. This study was determined that immunotherapy is more effective in low-m6Ascore PCa patients with poor prognosis.

Keywords: Immunotherapy; PCa; Tumor Immune Microenvironment; m6A; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / genetics
  • Adenosine / metabolism
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Clinical Decision-Making
  • Databases, Genetic
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / metabolism
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / metabolism*
  • RNA Processing, Post-Transcriptional*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Transcriptome
  • Tumor Microenvironment*
  • Tumor-Associated Macrophages / immunology
  • Tumor-Associated Macrophages / metabolism

Substances

  • Biomarkers, Tumor
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • Immune Checkpoint Inhibitors
  • Nuclear Proteins
  • RNA-Binding Proteins
  • VIRMA protein, human
  • ZC3H13 protein, human
  • N-methyladenosine
  • METTL14 protein, human
  • Methyltransferases
  • Adenosine