Gene-associated methylation status of ST14 as a predictor of survival and hormone receptor positivity in breast Cancer

BMC Cancer. 2021 Aug 21;21(1):945. doi: 10.1186/s12885-021-08645-3.

Abstract

Background: Genomic profiles of specific gene sets have been established to guide personalized treatment and prognosis for patients with breast cancer (BC). However, epigenomic information has not yet been applied in a clinical setting. ST14 encodes matriptase, a proteinase that is widely expressed in BC with reported prognostic value.

Methods: In this present study, we evaluated the effect of ST14 DNA methylation (DNAm) on overall survival (OS) of patients with BC as a representative example to promote the use of the epigenome in clinical decisions. We analyzed publicly available genomic and epigenomic data from 1361 BC patients. Methylation was characterized by the β-value from CpG probes based on sequencing with the Illumina Human 450 K platform.

Results: A high mean DNAm (β > 0.6779) across 34 CpG probes for ST14, as the gene-associated methylation (GAM) pattern, was associated with a longer OS after adjusting age, stage, histology and molecular features in Cox model (p value < 0.001). A high GAM status was also associated with a higher XBP1 expression level and higher proportion of hormone-positive BC (p value < 0.001). Pathway analysis revealed that altered GAM was related to matrisome-associated pathway.

Conclusions: Here we show the potential role of ST14 DNAm in BC prognosis and warrant further study.

Keywords: Breast Cancer; DNA methylation; Matriptase; ST14.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • DNA Methylation*
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Serine Endopeptidases / genetics*
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Serine Endopeptidases
  • ST14 protein, human