Identification of biomarkers related to Tumor-Infiltrating Lymphocytes (TILs) infiltration with gene co-expression network in colorectal cancer

Bioengineered. 2021 Dec;12(1):1676-1688. doi: 10.1080/21655979.2021.1921551.

Abstract

Colorectal cancer (CRC) is one of the most common tumors, ranking second in the global cause of death from cancer. The prognosis of advanced patients is still very poor. In this study, hub modules with the highest association with tumor-infiltrating immune cells were identified by weighted gene co-expression network analysis based on CRC expression data from the Gene Expression Omnibus database. Next, three hub genes (ADAM8, IL-1A, VAV3) related to infiltrating immune cells were identified by co-expression network and prognostic analysis. After analysis and verification of the TIMER database, ADAM8 was selected as a prognostic biomarker. Finally, the result of functional test showed that ADAM8 gene expression down-regulation partially reversed the immune tolerance of CRC cells to TILs. By bioinformatics analysis methods and the experimental techniques, we identified ADAM8 as a prognostic biomarker and clinical therapeutic target related to tumor-infiltrating immune cells in CRC.

Keywords: ADAM8; Colorectal cancer (CRC); TILs; TIMER; cibersort; weighted gene co-expression network analysis (WGCNA).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Death
  • Cell Line, Tumor
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Gene Regulatory Networks*
  • Genes, Neoplasm
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Membrane Proteins / genetics
  • Prognosis
  • Reproducibility of Results
  • Signal Transduction / genetics

Substances

  • Biomarkers, Tumor
  • Membrane Proteins
  • ADAM Proteins
  • ADAM8 protein, human

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 81874223).