Identification of the GTPase IMAP family as an immune-related prognostic biomarker in the breast cancer tumor microenvironment

Gene. 2022 Feb 20:812:146094. doi: 10.1016/j.gene.2021.146094. Epub 2021 Dec 9.

Abstract

Introduction: Breast cancer is the most common malignancy threatening women's health worldwide. The GTPase IMAP family genes are proteins belonging to the immune-associated nucleotide subfamily of the GTP-binding superfamily and nucleotide-binding proteins. However, little is known about the role of different GTPase IMAP family genes in breast cancer.

Methods: We obtained differential genes from the GEPIA and UALCAN databases and then used the Kaplan-Meier plotter, The Human Protein Atlas, NetworkAnalyst, STRING, and TIMER to analyze the prognostic value, protein expression, and immune cell infiltration of the GTPase IMAP family in patients with breast cancer.

Results: Among the GIMAP family genes, the expression levels of GIMAP1, GIMAP5, GIMAP6, GIMAP7, and GIMAP8 were significantly low in breast tumor tissues. In the overall population, patients with high expression of all genes of the GIMAP family had a significantly higher overall survival (OS), with the most significant increase correlated with the GIMAP2 gene (hazard ratio [HR] = 0.45, 95% confidence interval [CI], 0.34-0.59, P = 3.1e-09). However, patients with high expression of the GIMAP family genes in triple-negative breast cancer compared to those with low expression had a significant OS benefit, with the most pronounced benefit correlated with the GIMAP2 gene (HR = 0.37, 95% CI, 0.23-0.59, P = 1.4e-05). GIMAP7 and GIMAP8 were significantly upregulated in breast tumor tissues. The expression of genes in different GIMAP families was positively correlated with the infiltration and expression of six immune cell types (B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells).

Conclusion: This study may provide novel insights into the selection of GIMAP family prognostic biomarkers for breast cancer.

Keywords: Breast cancer; Immune-related; Prognostic; The GTPase IMAP family; Tumor microenvironment.

MeSH terms

  • B-Lymphocytes / metabolism
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes
  • Databases, Genetic
  • Female
  • GTP-Binding Proteins / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Multigene Family
  • Prognosis
  • Survival Analysis
  • Tumor Microenvironment

Substances

  • Biomarkers, Tumor
  • GTP-Binding Proteins