Clinicopathological and molecular significance of Sumolyation marker (ubiquitin conjugating enzyme 9 (UBC9)) expression in breast cancer of black women

Pathol Res Pract. 2014 Jan;210(1):10-7. doi: 10.1016/j.prp.2013.09.011. Epub 2013 Oct 8.

Abstract

The majority of breast cancers (BC) in Nigerian women are triple negative and show breast cancer-associated gene 1 (BRCA1) deficiency as well as the basal like phenotype, with a high mortality rate. In contrast to the well-defined predictive factors for the hormonal therapy, there is a paucity of information on the BRCA1 deficiency breast tumor biology, particularly among African women. BRCA1 Sumoylation (UBC9) has been speculated to be involved in the ER transcription activity, BRCA1 deficiency and triple negative BC. We therefore hypothesized that UBC9, a SUMOylation marker, may have contributed to the aggressive nature of BRCA1 tumor phenotype observed in Nigerian women. This study investigated the immunoprofiles of UBC9 in tissue microarray (TMA) of 199 Nigerian women and correlated their protein expression with clinical outcome, pathological responses and the expression of other biomarkers to demonstrate the functional significance in Nigerian women. The protein expression of UBC9, as compared with other biomarkers, showed an inverse correlation with steroid hormones (ER, progesterone (PgR)), BRCA1, p27, p21 and MDM4, and a positive correlation with triple negative, basal cytokeratins (CK14 and CK5/6), epidermal growth factor receptor (EGFR), basal-like breast cancer phenotype, p53, phosphoinositide-3-kinases (PI3KCA), placental cadherin, (P-cadherin) and BRCA1 regulators (metastasis tumor antigen-1 (MTA1). Survival analysis showed that those tumors positive for UBC9 expression had a significantly poorer breast cancer-specific survival (BCSS) as compared with those showing negative expression. UBC9 remained an independent predictor of outcome for BCSS. This study demonstrates that UBC9 appears to play an important role in the tumor biology of Nigerian women. Therefore, a novel UBC9 targeted therapy in black women with BC could enhance a better patient outcome.

Keywords: Black women; Breast cancer; Patient outcome; UBC9.

MeSH terms

  • Adult
  • African Continental Ancestry Group
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Nigeria
  • Tissue Array Analysis
  • Ubiquitin-Conjugating Enzymes / analysis
  • Ubiquitin-Conjugating Enzymes / biosynthesis*

Substances

  • Biomarkers, Tumor
  • Ubiquitin-Conjugating Enzymes
  • ubiquitin-conjugating enzyme UBC9