Screening of immunosuppressive cells from colorectal adenocarcinoma and identification of prognostic markers

Biosci Rep. 2021 Apr 30;41(4):BSR20203496. doi: 10.1042/BSR20203496.

Abstract

Background: Colorectal cancer (CRC) is the most common type of gastrointestinal malignant tumour. Colorectal adenocarcinoma (COAD) - the most common type of CRC - is particularly dangerous. The role of the immune system in the development of tumour-associated inflammation and cancer has received increasing attention recently.

Methods: In the present study, we compiled the expression profiles of 262 patients with complete follow-up data from The Cancer Genome Atlas (TCGA) database as an experimental group and selected 65 samples from the Gene Expression Omnibus (GEO) dataset (of which 46 samples were with M0) as a verification group. First, we screened the immune T helper 17 (Th17) cells related to the prognosis of COAD. Subsequently, we identified Th17 cells-related hub genes by utilising Weighted Gene Co-expression Network Analysis (WGCNA) and Least Absolute Shrinkage and Selector Operation (LASSO) regression analysis. Six genes associated with the prognosis in patients with COAD were identified, including: KRT23, ULBP2, ASRGL1, SERPINA1, SCIN, and SLC28A2. We constructed a clinical prediction model and analysed its predictive power.

Results: The identified hub genes are involved in developing many diseases and closely linked to digestive disorders. Our results suggested that the hub genes could influence the prognosis of COAD by regulating Th17 cells' infiltration.

Conclusions: These newly discovered hub genes contribute to clarifying the mechanisms of COAD development and metastasis. Given that they promote COAD development, they may become new therapeutic targets and biomarkers of COAD.

Keywords: COAD; Immunosuppressive cells; Th-17 cells.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / immunology
  • Adenocarcinoma / pathology
  • Asparaginase / genetics
  • Asparaginase / metabolism
  • Autoantigens / genetics
  • Autoantigens / metabolism
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / immunology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / pathology
  • Computational Biology
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Gelsolin / genetics
  • Gelsolin / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Keratins, Type I / genetics
  • Keratins, Type I / metabolism
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Th17 Cells / immunology*
  • alpha 1-Antitrypsin / genetics
  • alpha 1-Antitrypsin / metabolism

Substances

  • Autoantigens
  • Biomarkers, Tumor
  • GPI-Linked Proteins
  • Gelsolin
  • Intercellular Signaling Peptides and Proteins
  • KRT23 protein, human
  • Keratins, Type I
  • Membrane Transport Proteins
  • SERPINA1 protein, human
  • ULBP2 protein, human
  • alpha 1-Antitrypsin
  • cif nucleoside transporter
  • scinderin
  • ASRGL1 protein, human
  • Asparaginase