KRAS expression is a prognostic indicator and associated with immune infiltration in breast cancer

Breast Cancer. 2021 Mar;28(2):379-386. doi: 10.1007/s12282-020-01170-4. Epub 2020 Oct 16.

Abstract

Background: Breast cancer is the most common cancer and the leading cause of death among women. KRAS is known as an oncogene, its expression also associates with cancer prognosis. The purpose of this study was to investigate the prognostic value of KRAS expression in breast cancer and its relationship with immune infiltration.

Methods: Firstly, the expression level and methylation of KRAS were analyzed. Then survival analysis was used to verify the prognostic capability of KRAS expression. After that, gene functional enrichment analysis was performed. The relationship between KRAS gene expression and immune infiltration was researched later.

Results: The expression level of KRAS in breast cancer was increased (P = 2.2e-16). Tumor KRAS expression in the subtypes of basal-like, HER2-enriched, Luminal A and Luminal B were 1.64, 1.67, 1.51 and 1.42 times of normal, respectively. 13 methylation sites were different between tumor and normal tissues and associated with KRAS expression. Subsequently, Kaplan-Meier analysis suggested that the high KRAS expression group had a poor prognosis (P = 0.0028). In multivariate Cox regression analysis, KRAS expression was an independent prognostic indicator (HR = 1.353, 95% CI 1.009-1.814, P = 0.044). Gene Ontology (GO) analysis showed enrichment of epidermal growth associated pathways. Additionally, different KRAS expression levels represented different tumor immune infiltration status, which may be caused by the influence of the RAS/MAPK and RAS/PI3K pathways on the level of PD-L1.

Conclusion: This study suggests that KRAS expression can be used as a prognostic indicator of breast cancer, and it is closely related to tumor immune infiltration.

Keywords: Biomarker; Breast cancer; Immune infiltration; KRAS expression; Prognosis.

MeSH terms

  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Case-Control Studies
  • Cohort Studies
  • Computational Biology / methods
  • DNA Methylation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Proto-Oncogene Proteins p21(ras) / metabolism*
  • Proto-Oncogenes*
  • T-Lymphocytes, Regulatory / immunology
  • Tumor Microenvironment / immunology*

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • KRAS protein, human
  • Proto-Oncogene Proteins p21(ras)