Development of a Novel Prognostic Signature Based on Antigen Processing and Presentation in Patients with Breast Cancer

Pathol Oncol Res. 2021 Apr 1:27:600727. doi: 10.3389/pore.2021.600727. eCollection 2021.

Abstract

Background: Complex antigen processing and presentation processes are involved in the development and progression of breast cancer (BC). A single biomarker is unlikely to adequately reflect the complex interplay between immune cells and cancer; however, there have been few attempts to find a robust antigen processing and presentation-related signature to predict the survival outcome of BC patients with respect to tumor immunology. Therefore, we aimed to develop an accurate gene signature based on immune-related genes for prognosis prediction of BC. Methods: Information on BC patients was obtained from The Cancer Genome Atlas. Gene set enrichment analysis was used to confirm the gene set related to antigen processing and presentation that contributed to BC. Cox proportional regression, multivariate Cox regression, and stratified analysis were used to identify the prognostic power of the gene signature. Differentially expressed mRNAs between high- and low-risk groups were determined by KEGG analysis. Results: A three-gene signature comprising HSPA5 (heat shock protein family A member 5), PSME2 (proteasome activator subunit 2), and HLA-F (major histocompatibility complex, class I, F) was significantly associated with OS. HSPA5 and PSME2 were protective (hazard ratio (HR) < 1), and HLA-F was risky (HR > 1). Risk score, estrogen receptor (ER), progesterone receptor (PR) and PD-L1 were independent prognostic indicators. KIT and ACACB may have important roles in the mechanism by which the gene signature regulates prognosis of BC. Conclusion: The proposed three-gene signature is a promising biomarker for estimating survival outcomes in BC patients.

Keywords: antigen processing and presentation; breast cancer; cell biology; prognostic; survival.

MeSH terms

  • Antigen Presentation*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / immunology
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Endoplasmic Reticulum Chaperone BiP / genetics
  • Endoplasmic Reticulum Chaperone BiP / metabolism*
  • Female
  • Follow-Up Studies
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Middle Aged
  • Prognosis
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism*
  • Survival Rate
  • Transcriptome

Substances

  • Biomarkers, Tumor
  • Endoplasmic Reticulum Chaperone BiP
  • HLA-F antigens
  • HSPA5 protein, human
  • Histocompatibility Antigens Class I
  • PSME2 protein, human
  • Proteasome Endopeptidase Complex