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.
Department of Surgery, Olabisi Onabanjo University, Sagamu, Nigeria.
Pathol Res Pract. 2014 Jan;210(1):10-7. doi: 10.1016/j.prp.2013.09.011. Epub 2013 Oct 8.
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.
大多数尼日利亚妇女的乳腺癌（BC）是三阴性的，并且表现出乳腺癌相关基因 1（BRCA1）缺陷以及基底样表型，死亡率很高。与激素治疗的明确预测因素相比，BRCA1 缺陷性乳腺癌生物学方面的信息很少，特别是在非洲妇女中。BRCA1 聚泛素化（UBC9）被推测参与 ER 转录活性、BRCA1 缺陷和三阴性 BC。因此，我们假设 UBC9，一种 SUMOylation 标志物，可能导致在尼日利亚妇女中观察到的 BRCA1 肿瘤表型的侵袭性。本研究调查了组织微阵列（TMA）中 199 名尼日利亚妇女的 UBC9 免疫组化，并将其蛋白表达与临床结局、病理反应以及其他生物标志物的表达相关联，以证明其在尼日利亚妇女中的功能意义。与其他生物标志物相比，UBC9 的蛋白表达与甾体激素（ER、孕激素（PgR））、BRCA1、p27、p21 和 MDM4 呈负相关，与三阴性、基底细胞角蛋白（CK14 和 CK5/6）、表皮生长因子受体（EGFR）、基底样乳腺癌表型、p53、磷酸肌醇-3-激酶（PI3KCA）、胎盘钙黏蛋白（P-cadherin）和 BRCA1 调节剂（转移肿瘤抗原-1（MTA1）呈正相关。生存分析表明，与表达 UBC9 阴性的肿瘤相比，表达 UBC9 的肿瘤乳腺癌特异性生存率（BCSS）显著更差。UBC9 仍然是 BCSS 的独立预后因素。本研究表明，UBC9 似乎在尼日利亚妇女的肿瘤生物学中发挥重要作用。因此，针对黑人妇女的 BC 进行新型 UBC9 靶向治疗可能会改善患者预后。
