AKR1B10 regulates M2 macrophage polarization to promote the malignant phenotype of gastric cancer

Biosci Rep. 2023 Oct 31;43(10):BSR20222007. doi: 10.1042/BSR20222007.

Abstract

Background: Immunotherapy has brought new hope to gastric cancer (GC) patients. Exploring the immune infiltration pattern in GC and the key molecules is critical for optimizing the efficacy of immunotherapy. Aldo-keto reductase family 1 member B10 (AKR1B10) is an inflammatory regulator and is closely related to the prognosis of patients with GC. However, the function of AKR1B10 in GC remains unclear.

Methods: In the present study, the CIBERSORT algorithm was used to analyze the immune infiltration pattern in 373 samples in the Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were seared by combing the TCGA database and the Gene Expression Omnibus (GEO) database, and the key molecule AKR1B10 was identified by weighted gene coexpression network analysis (WGCNA). The biological functions of AKR1B10 in stomach adenocarcinoma (STAD) were investigated in vitro.

Results: Macrophage polarization was the main immune infiltration pattern in GC, and the state of macrophage polarization was closely related to the pathological grading of GC and the clinical stage of patients. AKR1B10, MUC5AC, TFF2, GKN1, and PGC were significantly down-regulated in GC tissues. Low AKR1B10 expression induced M2 macrophage polarization and promoted the malignant phenotype of GC.

Conclusion: M2 macrophage polarization is the main immune infiltration pattern in GC. Low AKR1B10 expression induces M2 macrophage polarization and promotes the malignant transformation of GC.

Keywords: AKR1B10; Immune infiltration; M2 macrophage polarization; WGCNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldo-Keto Reductases / genetics
  • Aldo-Keto Reductases / metabolism
  • Humans
  • Macrophages / metabolism
  • Peptide Hormones*
  • Phenotype
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / pathology

Substances

  • Aldo-Keto Reductases
  • AKR1B10 protein, human
  • GKN1 protein, human
  • Peptide Hormones