Multi-omics analysis of the expression and prognostic value of the butyrophilins in breast cancer

J Leukoc Biol. 2021 Dec;110(6):1181-1195. doi: 10.1002/JLB.5MA0321-158RR. Epub 2021 Aug 19.

Abstract

Butyrophilins (BTNs) belong to the immunoglobulin superfamily of transmembrane proteins and play a role in the regulation of lymphocyte activation, several autoimmune diseases, and the progression of human cancers. However, the associated clinicopathologic characteristics and prognostic value of BTNs in breast cancer remain unknown. This study aimed to discover potential key related BTN genes and signaling pathways in breast cancer, which could provide new insights for immune-based strategies. In the present study, the mRNA expression level and prognostic value of BTN2A1, BTN3A1, BTN3A2, BTN3A3, BTNL2, BTNL9, ERMAP, and MOG were measured. Up-regulation of these genes was significantly correlated with improved overall and relapse-free survival. We then analyzed the prognostic outcomes of breast cancer subtypes, genetic alterations, interaction networks, and the functional enrichment of eight BTN family genes. Our results showed that these eight genes played essential roles in tumor progression. Furthermore, an immune infiltration analysis indicated that most candidate BTN family members were associated with intratumoral immune cell infiltration, especially that of γδ T cells. Finally, gene set enrichment analysis for a single hub gene revealed that each BTN gene played a vital role in tumor progression through immune signaling pathways. These findings provided new insights into breast cancer pathogenesis and identified eight potential biomarkers for breast cancer.

Keywords: breast cancer; butyrophilins; prognostic value; signaling pathways; tumor-immune cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / immunology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / metabolism
  • Butyrophilins / biosynthesis
  • Butyrophilins / genetics
  • Butyrophilins / immunology*
  • Female
  • Genomics
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Middle Aged
  • Prognosis
  • Proteomics
  • Transcriptome

Substances

  • Biomarkers, Tumor
  • Butyrophilins