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首页> 外文期刊>Journal of Cancer Research and Treatment >BRCA1 Protein Deficiency in Breast Cancer Microbiopsy Lysate Delineates Patient Survival Time
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BRCA1 Protein Deficiency in Breast Cancer Microbiopsy Lysate Delineates Patient Survival Time

机译：BRCA1乳腺癌微生物溶液裂解物描绘患者存活时间

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Introduction: Breast-Cancer gene 1(BRCA1) encodes for protein which has many cellular functions including DNA damage repair and maintenance of genome integrity. Malfunction or deficiency of BRCA1 protein, due to mutations or epigenetic inactivation, may provoke breast epithelial cell dedifferentiation and initiate cancer. In fact, mutants of BRCA1 predispose to breast and ovarian cancers. In the past this biomarker was not investigated for breast cancer prevention and care in Benin. The aim of our work is to assess the expression pattern of BRCA1 gene and protein in precancerous and cancerous breast tissue microbiopsies to determine the molecular mechanisms underlying BRCA1 protein suppression and potentiate prognosis and targeted personalized therapy in Benin. Method: This study obtains the institutional ethical approval. Microbiopsy tissues (n = 54) were collected in the Visceral surgery department of the National University Hospital Center HKM (CNHU-HKM) located in the city of Cotonou (Benin) for diagnosis and prognosis purposes. Polymerase chain reaction (PCR) technic with primers targeting Exon 1 and Exon 2 of BRCA1 was used to assess gene transcription capability. Immunoblotting was used to determine BRCA1 protein profile in breast cancer tissue microbiopsy lysates. Ethical approval was obtained for this study. Kaplan–Meier curves analysis was performed to determine the median survival time according to BRCA1 gene and protein patterns. Results: We observed that 87% of samples had lost the expression of BRCA1 protein. Among them, 78% of the loss was not associated to gene deletion. The disparity between the presence of the BRCA1 gene and the lack of protein expression suggested that the silencing of BRCA1 may be due to epigenetic inactivation in most patients. Ultimately, Kaplan Meyer’s survival curve analysis showed that the lack of BRCA1 amplification at Exon 1 or Exon 2 diminished the median survival time of cancer patients to 20 months. Conclusion: BRCA1 protein translation is impaired by Exon 1 or Exon 2 mutation /deletion along with epigenetic inactivation in breast cancer; all together influences median survival time. The delineation of the molecular mechanism underlying BRCA1 gene inactivation leading to protein deficiency will be an excellent molecular tool for African breast cancer prognostic and personalized targeted therapy in the future.
机译：简介：乳腺癌基因1（BRCA1）编码蛋白质，其具有许多细胞功能，包括DNA损伤修复和基因组完整性的维持。由于突变或表观遗传灭活，BRCA1蛋白的故障或缺乏，可能会引发乳房上皮细胞去消除和引发癌症。事实上，BRCA1的突变体易于乳腺癌和卵巢癌。在过去，这种生物标志物未对贝宁进行乳腺癌预防和护理。我们作品的目的是评估BRCA1基因和蛋白质在癌前和癌乳腺组织微生物中的表达模式，以确定BRCA1蛋白抑制和增强性预后的分子机制和贝宁的靶向个性化治疗。方法：本研究获得了制度伦理批准。在国立大学医院中心HKM（CNHU-HKM）的内脏外科部门（CNHU-HKM）的内部手术部门收集了微生物缺血组织（N = 54），位于Cotonou（贝宁）市，以诊断和预后目的。使用具有BRCA1的引物的聚合酶链反应（PCR）技术，用于评估基因转录能力。免疫印迹用于测定乳腺癌组织微生物缺酸盐中的BRCA1蛋白质谱。本研究获得了道德认可。考虑Kaplan-Meier曲线分析以确定根据BRCA1基因和蛋白质模式的中值存活时间。结果：我们观察到87％的样品失去了BRCA1蛋白的表达。其中，78％的损失与基因缺失无关。 BRCA1基因的存在与缺乏蛋白质表达的差异表明BRCA1的沉默可能是由于大多数患者的表观遗传失活。最终，Kaplan Meyer的存活曲线分析表明，外显子1或外显子2的BRCA1扩增缺乏将癌症患者的中位生存时间减少到20个月。结论：BRCA1蛋白翻译因外显子1或外显子2突变/缺失以及乳腺癌中的表观遗传失活而受到损害;全部影响中位生存时间。 BRCA1基因灭活的分子机制划分导致蛋白质缺陷的分子机制将是未来非洲乳腺癌预后和个性化靶向治疗的优秀分子工具。

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