Identification of a novel immune prognostic model in gastric cancer

Clin Transl Oncol. 2021 Apr;23(4):846-855. doi: 10.1007/s12094-020-02478-5. Epub 2020 Aug 28.

Abstract

Purpose: The tumor immune microenvironment (TIME) is now considered as an important factor during gastric cancer (GC) development. This study identified a novel immune-related risk model for predicting prognosis and assessing the immune status of GC patients.

Methods: Transcriptomic data were obtained from the TCGA database. The differential expressed immune-related genes (IRGs) were identified through the ImmPort portal. Enrichment analysis was performed to explore the potential molecular mechanism of these IRGs. By the Cox regression analysis, we constructed the immune prognostic model. Then, the association between the model and the immune microenvironment was estimated. The model was validated in the GSE84433 dataset.

Results: Totally, we identified 222 differentially expressed IRGs. These IRGs were closely correlated with immune response and immune signaling pathways. Through the Cox regression analysis, we developed the immune prognostic model based on the expression of seven IRGs (CXCL3, NOX4, PROC, FAM19A4, RNASE2, IGHD2-15, CGB5). Patients were stratified into two groups according to immune-related risk scores. Survival analysis indicated that the prognosis of high-risk patients was poorer than low-risk patients. Moreover, the immune-related risk score was an independent prognostic biomarker. More importantly, we found that the infiltration level of immunosuppressive cells and the expression of inhibitory immune checkpoints were higher in high-risk patients. The immune microenvironment tended to be a suppressive status in patients with high-risk scores.

Conclusion: This study demonstrated that our model had predictive value for prognosis and the TIME in GC. It might be a robust tool to improve personalized patient management.

Keywords: Gastric cancer; Immune-related gene; Model; Prognosis; Tumor immune microenvironment.

MeSH terms

  • Chemokines, CXC / genetics
  • Cytokines / genetics
  • Databases, Genetic
  • Disease Progression
  • Dwarfism, Pituitary / genetics
  • Eosinophil-Derived Neurotoxin / genetics
  • Gene Expression / immunology
  • Humans
  • Immune Checkpoint Proteins / metabolism
  • Immune Tolerance / genetics
  • Immunity / genetics*
  • Models, Immunological*
  • NADPH Oxidase 4 / genetics
  • Neoplastic Stem Cells / immunology
  • Prognosis
  • Regression Analysis
  • Risk Factors
  • Stomach Neoplasms / immunology*
  • Stomach Neoplasms / mortality
  • Survival Analysis
  • Transcriptome
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology*

Substances

  • CXCL3 protein, human
  • Chemokines, CXC
  • Cytokines
  • Immune Checkpoint Proteins
  • TAFA4 protein, human
  • NADPH Oxidase 4
  • NOX4 protein, human
  • Eosinophil-Derived Neurotoxin
  • RNASE2 protein, human

Supplementary concepts

  • Isolated Growth Hormone Deficiency, Type II