title: Clinicopathological and molecular significance of Sumolyation marker (ubiquitin conjugating enzyme 9 (UBC9)) expression in breast cancer of black women.
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.
authors.affiliation: Division of Pathology, School of Molecular Medical Sciences, Nottingham University Hospitals and University of Nottingham, Nottingham, United Kingdom; Department of Morbid Anatomy and Histopathology, Olabisi Onabanjo University, Sagamu, Nigeria.
authors.forename: A O J
authors.initials: AO
authors.lastname: Agboola
authors.affiliation: Department of Surgery, Olabisi Onabanjo University, Sagamu, Nigeria.
authors.forename: A A
authors.initials: AA
authors.lastname: Musa
authors.affiliation: Department of Surgery, Olabisi Onabanjo University, Sagamu, Nigeria.
authors.forename: B A
authors.initials: BA
authors.lastname: Ayoade
authors.affiliation: Department of Morbid Anatomy and Histopathology, Olabisi Onabanjo University, Sagamu, Nigeria.
authors.forename: A A
authors.initials: AA
authors.lastname: Banjo
authors.affiliation: Department of Morbid Anatomy and Histopathology, Olabisi Onabanjo University, Sagamu, Nigeria.
authors.forename: C C
authors.initials: CC
authors.lastname: Anunobi
authors.affiliation: Department of Medical Microbiology Parasitology, Olabisi Onabanjo University, Sagamu, Nigeria.
authors.forename: A M
authors.initials: AM
authors.lastname: Deji-Agboola
authors.affiliation: Division of Pathology, School of Molecular Medical Sciences, Nottingham University Hospitals and University of Nottingham, Nottingham, United Kingdom.
authors.forename: E A
authors.initials: EA
authors.lastname: Rakha
authors.affiliation: Division of Pathology, School of Molecular Medical Sciences, Nottingham University Hospitals and University of Nottingham, Nottingham, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Nolan
authors.affiliation: Division of Pathology, School of Molecular Medical Sciences, Nottingham University Hospitals and University of Nottingham, Nottingham, United Kingdom.
authors.forename: I O
authors.initials: IO
authors.lastname: Ellis
authors.affiliation: Division of Pathology, School of Molecular Medical Sciences, Nottingham University Hospitals and University of Nottingham, Nottingham, United Kingdom.
authors.forename: A R
authors.initials: AR
authors.lastname: Green
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D044383:Black People; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009549:Nigeria; D046888:Tissue Array Analysis; D044763:Ubiquitin-Conjugating Enzymes / Q000032:analysis / Q000096:biosynthesis*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D014408:Biomarkers, Tumor; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9
keywords: Black women; Breast cancer; Patient outcome; UBC9