Histone Deacetylase 7 Gene Overexpression Is Associated with Poor Prognosis of Triple-Negative Breast Cancer Patients

Genet Test Mol Biomarkers. 2021 Mar;25(3):227-235. doi: 10.1089/gtmb.2020.0138.

Abstract

Background: Differential expressions of cancer-associated genes, including histone deacetylases (HDACs), were identified in distinctive molecular subtypes of breast cancer. Compared with hormone receptor-positive breast cancer, triple-negative (TNBC, ER-PR-HER2-) is the most aggressive form of breast cancer. Aims: To determine the association of HDAC7 mRNA expression levels with clinicopathological features and patients' survival with TNBC or ER+PR+HER2- breast cancers. Methods: Total RNA was extracted from 61 TNBC and 74 ER+PR+Her2- tumors. Relative gene expression was evaluated by SYBR Green RT-PCR, normalized to glyceraldehyde-3-phosphate dehydrogenase. The HDAC7 mRNA expression was defined as high or low, according to receiver operating characteristic analysis. Kaplan-Meier and Cox regression analyses for overall survival were assessed to evaluate the prognostic relevance of HDAC7 overexpression. Results: The HDAC7 overexpression was predominantly found in invasive ductal carcinomas (p = 0.023), high histologic grade (p = 0.007), and high nuclear grade tumors (p = 0.030). TNBC subtypes had a significantly lower mean HDAC7 gene expression compared with ER+PR+HER2- tumors (p = 0.005). However, HDAC7 overexpression predicted unfavorable survival of TNBC patients (p = 0.003). Multivariate Cox regression analysis indicated that recurrences (hazard ratio [HR] = 5.432, p = 0.003), and HDAC7 overexpression (HR = 9.287, p = 0.033) persisted as independent prognostic factors for poor survival of TNBC patients. Conclusions: HDAC7 mRNA overexpression is associated with poor survival in patients with TNBC tumors.

Keywords: gene expression; histon deacetylase 7; hormone receptor-positive breast cancer; survival; triple-negative breast cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Disease-Free Survival
  • Female
  • Gene Expression / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Histone Deacetylases / genetics*
  • Histone Deacetylases / metabolism
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics
  • Prognosis
  • Proportional Hazards Models
  • Receptor, ErbB-2 / genetics
  • Receptors, Progesterone / genetics
  • Serbia
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / metabolism

Substances

  • Biomarkers, Tumor
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • HDAC7 protein, human
  • Histone Deacetylases