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首页> 外文期刊>Journal of Cancer Research and Treatment >Clinical and Molecular Significance of Poly (ADP-Ribose) Polymerase-1 (PARP-1) in Breast Cancer of African Women and its Potential as a Targeted Therapy
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Clinical and Molecular Significance of Poly (ADP-Ribose) Polymerase-1 (PARP-1) in Breast Cancer of African Women and its Potential as a Targeted Therapy

机译：聚（ADP-核糖）聚合酶-1（PARP-1）在非洲女性乳腺癌中的临床和分子意义及其作为靶向治疗的潜力

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Background: The therapeutic effects of Poly (ADP-ribose) polymerase-1 (PARP -1) inhibition are currently studied in a clinical trial that is recruiting African- American (A-A) women with breast cancer (BC). Although, A-A and West African women are likely to share the same ancestry, there are overwhelming evidences, that BC is undoubtedly heterogeneous which might influence results obtained in these Nationalities. Thus, this study aims to investigate PARP-1 expression in a large and annotated series of breast cancer from Nigerian women to determine its clinical and biological significance for the indigenous African women. Methods: PARP-1 protein expression was assessed immunohistochemically in 204 formalin fixed paraffin samples from Nigerian breast cancer women prepared as TMA. Results: PARP-1 was inversely associated with steroid hormone receptors (oestrogen (ER) and progesterone (PR) receptor), the Homologous Recombination marker BRCA1 associated ring domain 1 (BARD1) and p27. Conversely, a positive association was established between PARP-1 and high histologic grade, expression of basal markers (cytokeratins (CK) 5/6 and 14) and epidermal growth factor receptor (EGFR)), DNA damage-repair markers (protein inhibitor of activator signal transducer gamma (PIAS)), the BRCA1 inhibitor (metastasis tumour antigen-1 (MTA1), p53, the proliferation markers (KI-67, Phosphoinositide-3-kinases (PI3KCA)), the triple-negative and basal-like phenotypes. Outcome analysis indicated PARP-1 as a predictor of poor survival independent of tumour size, histological grade and lymph node involvement. Conclusion: These results provide evidence that PARP-1 plays an important role in Nigerian women with breast cancer. It is recommended that indigenous Black women from Africa are included in the ongoing clinical trial of PARP1 inhibitors that is aimed at determining the efficiency of the drug in black BC women outside United States.
机译：背景：聚（ADP-核糖）聚合酶-1（PARP -1）抑制的治疗作用目前正在一项临床试验中进行研究，该试验招募了患有乳腺癌（BC）的非裔美国人（A-A）妇女。尽管A-A和西非妇女可能有着相同的血统，但有大量证据表明，BC无疑是异质的，这可能会影响到这些民族的研究结果。因此，本研究旨在调查PARP-1在来自尼日利亚妇女的一系列大型且带注释的乳腺癌中的表达，以确定其对非洲土著妇女的临床和生物学意义。方法：采用免疫组织化学方法对204例福尔马林固定石蜡样本中的TMA进行了免疫组化分析，以评估PARP-1蛋白的表达。结果：PARP-1与类固醇激素受体（雌激素（ER）和孕激素（PR）受体），同源重组标记BRCA1相关的环域1（BARD1）和p27反向相关。相反，在PARP-1与高组织学等级，基础标志物（细胞角蛋白（CK）5/6和14）和表皮生长因子受体（EGFR）的表达，DNA损伤修复标志物（蛋白抑制剂）之间建立了正相关。激活信号转导物γ（PIAS）），BRCA1抑制剂（转移瘤抗原1（MTA1），p53，增殖标志物（KI-67，磷酸肌醇3激酶（PI3KCA）），三阴性和基底样结果分析表明，PARP-1是不良生存率的预测指标，与肿瘤大小，组织学分级和淋巴结受累无关，其结论：这些结果提供了证据，表明PARP-1在尼日利亚女性乳腺癌中起重要作用，建议正在进行的PARP1抑制剂临床试验中包括了来自非洲的土著黑人妇女，该试验旨在确定该药物在美国以外的黑人BC妇女中的功效。

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