High Expression of the Component 3a Receptor 1 (C3AR1) Gene in Stomach Adenocarcinomas Infers a Poor Prognosis and High Immune-Infiltration Levels

Med Sci Monit. 2021 Feb 4:27:e927977. doi: 10.12659/MSM.927977.

Abstract

BACKGROUND This study was designed to explore the incompletely investigated role of the complement component 3a receptor 1 (C3AR1) in the prognosis of stomach adenocarcinomas (STAD). MATERIAL AND METHODS Using bioinformatic methods, we systematically determined the expression and prognosis value of C3AR1 in various cancers by using the TIMER (Tumor Immune Estimation Resource) database, UALCAN platform, GEPIA (Gene Expression Profiling Interactive Analysis) server, and the OncoLnc tool. The biological processes influenced by C3AR1 were determined using the GSEA (Gene Set Enrichment Analysis) software (Copyright 2004-2020 Broad Institute, Inc., Massachusetts Institute of Technology, and Regents of the University of California). The correlation between C3AR1 expression and the immune-infiltrating cells as well as the correlation analysis between C3AR1 expression and the corresponding immune-marker sets were conducted using the TIMER and GEPIA databases. RESULTS The expression of C3AR1 was significantly (P<0.001) differentially expressed on several tumor types, while its prognosis value could only be determined on STAD, with a high expression of C3AR1 closely correlated with a poor prognosis. The GSEA analysis revealed that the differential expression of C3AR1 profoundly affected the immune-related biological processes. The expression of C3AR1 was strongly and positively correlated with the infiltration of monocytes, tumor-associated macrophages, M2 macrophages, dendritic cells, and exhausted T cells. CONCLUSIONS Our results have revealed that a high expression of C3AR1 is positively correlated with a poor prognosis and increased tumor-immune infiltration. C3AR1 can promote the polarization of M2 macrophages and T cell exhaustion, leading to the immune escape of STAD. These findings suggest that C3AR1 could be used as a prognostic and immune-infiltration marker in the pathogenesis of STAD.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Biomarkers, Tumor / genetics
  • Computational Biology / methods
  • Databases, Genetic
  • Gene Expression / genetics
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Prognosis
  • Receptors, Complement / genetics*
  • Receptors, Complement / metabolism
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology*
  • Transcriptome / genetics

Substances

  • Biomarkers, Tumor
  • Receptors, Complement
  • complement C3a receptor