GNG4, as a potential predictor of prognosis, is correlated with immune infiltrates in colon adenocarcinoma

J Cell Mol Med. 2023 Sep;27(17):2517-2532. doi: 10.1111/jcmm.17847. Epub 2023 Jul 13.

Abstract

The tumour microenvironment (TME) and immunosuppression play an important role in colon cancer (CC) metastasis, which seriously affects the prognosis of CC. G protein subunit gamma 4 (GNG4) has been shown to participate in tumour progression and the tumour mutation burden (TMB) in colorectal cancer. However, the effect of GNG4 on the CC TME and immunology remains elusive. Weighted gene coexpression network analysis (WGCNA) was employed for screening aberrantly expressed genes associated with the immune score, and GNG4 was then selected through prognostic and immune correlation analysis. Based on RNA sequencing data obtained from the TCGA and GEO databases, the expression pattern and immune characteristics of GNG4 were comprehensively examined using a pan-cancer analysis. Upregulation of GNG4 was linked to an adverse prognosis and immune inhibitory phenotype in CC. Pan-cancer analysis demonstrated higher GNG4 expression in tumours than in paired normal tissue in human cancers. GNG4 expression was closely related to prognosis, TMB, immune checkpoints (ICPs), microsatellite instability (MSI) and neoantigens. GNG4 promoted CC cell proliferation, migration and invasion and participated in immune regulation in the TME. Significantly, GNG4 expression was found to negatively correlate with tumour-infiltrating immune cells, ICP, TMB and MSI in CC. GNG4 expression predicted the immunotherapy response in the IMvigor210 cohort, suggesting that GNG4 could be used as a potential biomarker in CC for prognostication and immunology. Moreover, the expression of GNG4 predicted the immunotherapy response of ICB in CC.

Keywords: GNG4; colon cancer; immune infiltration; immunotherapy; tumour microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma* / diagnosis
  • Adenocarcinoma* / genetics
  • Cell Proliferation / genetics
  • Colonic Neoplasms* / diagnosis
  • Colonic Neoplasms* / genetics
  • Databases, Factual
  • Gene Regulatory Networks
  • Humans
  • Microsatellite Instability
  • Tumor Microenvironment / genetics