Identifying hub genes of clear cell renal cell carcinoma associated with the proportion of regulatory T cells by weighted gene co-expression network analysis

Aging (Albany NY). 2019 Oct 31;11(21):9478-9491. doi: 10.18632/aging.102397. Epub 2019 Oct 31.

Abstract

Background: Numerous patients with clear cell renal cell carcinoma (ccRCC) experience drug resistance after immunotherapy. Regulatory T (Treg) cells may work as a suppressor for anti-tumor immune response.

Purpose: We performed bioinformatics analysis to better understand the role of Treg cells in ccRCC.

Results: Module 10 revealed the most relevance with Treg cells. Functional annotation showed that biological processes and pathways were mainly related to activation of the immune system and the processes of immunoreaction. Four hub genes were selected: LCK, MAP4K1, SLAMF6, and RHOH. Further validation showed that the four hub genes well-distinguished tumor and normal tissues and were good prognostic biomarkers for ccRCC.

Conclusion: The identified hub genes facilitate our knowledge of the underlying molecular mechanism of how Treg cells affect ccRCC in anti-tumor immune therapy.

Methods: The CIBERSORT algorithm was performed to evaluate tumor-infiltrating immune cells based on the Cancer Genome Atlas cohort. Weighted gene co-expression network analysis was conducted to explore the modules related to Treg cells. Gene Ontology analysis and pathway enrichment analysis were performed for functional annotation and a protein-protein interaction network was built. Samples from the International Cancer Genomics Consortium database was used as a validation set.

Keywords: Treg cells; anti-tumor immune; ccRCC; hub genes; weighted gene co-expression network analysis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Algorithms
  • Biomarkers, Tumor
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / mortality
  • Female
  • Gene Regulatory Networks
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / immunology
  • Kidney Neoplasms / mortality
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / genetics
  • Male
  • Middle Aged
  • Protein Interaction Maps
  • Protein Serine-Threonine Kinases / genetics
  • Signaling Lymphocytic Activation Molecule Family / genetics
  • T-Lymphocytes, Regulatory*
  • Transcription Factors / genetics
  • rho GTP-Binding Proteins / genetics

Substances

  • Biomarkers, Tumor
  • RhoH protein, human
  • SLAMF6 protein, human
  • Signaling Lymphocytic Activation Molecule Family
  • Transcription Factors
  • hematopoietic progenitor kinase 1
  • LCK protein, human
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Protein Serine-Threonine Kinases
  • rho GTP-Binding Proteins