Department of Cancer Genetics, Istanbul Faculty of Medicine, Oncology Institute, Istanbul University, Istanbul, Turkey.
J Ovarian Res. 2020 Aug 27;13(1):99. doi: 10.1186/s13048-020-00706-8.
Ovarian cancer is the second most common gynecologic cancer with high mortality rate and generally diagnosed in advanced stages. The 5-year disease-free survival is below 40%. MicroRNAs, subset of the non-coding RNA molecules, regulate the translation in post transcriptional level by binding to specific mRNAs to promote or degrade the target oncogenes or tumor suppressor genes. Abnormal expression of miRNAs were found in numerous human cancer, including ovarian cancer. Investigating the miRNAs derived from the peripheral blood samples can be used as a marker in the diagnose, treatment and prognosis of ovarian cancer. We aimed to find biological markers for early diagnosis of ovarian cancer by investigating BRCA1 gene mutation carrier monozygotic discordant twins and their high risk healthy family individual's miRNAs.
The study was conducted on monozygotic twins discordant for ovarian cancer, and the liquid biopsy exploration of miRNAs was performed on mononuclear cells that were isolated from the peripheral blood samples. The miRNA expression profile changes in the study were found by using microarray analysis. miRNA isolation procedure performed from the lymphocyte in accordance with the kit protocol. The presence and quality of the isolated miRNAs screened by electrophoresis. Raw data logarithmic analysis was studied by identifying the threshold, normalization, correlation, mean and median values. Target proteins were detected for each miRNA by using different algorithms.
After the comparison of monozygotic discordant twins for epithelial ovarian carcinoma upregulation of the 4 miRNAs, miR-6131, miR-1305, miR-197-3p, miR-3651 and downregulation of 4 miRNAs, miR-3135b, miR-4430, miR-664b-5p, miR-766-3p were found statically significant.
The detected 99 miRNAs out of 2549 miRNAs might be used in the clinic as new biological indicators in the diagnosis and follow up of epithelial ovarian cancer with complementary studies. The miRNA expression profiles were identified to be statistically significant in the evaluation of ovarian cancer etiology, BRCA1 mutation status, and ovarian cancer risk in accordance with the obtained data. There is a need for validation of the miRNAs which were particularly detected between monozygotic twins and its association with ovarian cancer was emphasized in our study in wider cohorts including ovarian cancer patients, and healthy individuals.
卵巢癌是第二常见的妇科癌症，死亡率高，通常在晚期诊断。5 年无病生存率低于 40%。miRNA 是一类非编码 RNA 分子，通过与特定的 mRNAs 结合来促进或降解靶基因，从而在转录后水平上调节翻译。在许多人类癌症中，包括卵巢癌，都发现了 miRNA 的异常表达。研究来自外周血样本的 miRNA 可以作为卵巢癌诊断、治疗和预后的标志物。我们旨在通过研究 BRCA1 基因突变携带者的同卵双胞胎和他们的高危健康家族个体的 miRNA，找到卵巢癌早期诊断的生物学标志物。
本研究对卵巢癌不一致的同卵双胞胎进行了研究，并对外周血单核细胞进行了液体活检，以检测 miRNA。通过微阵列分析发现 miRNA 表达谱的变化。根据试剂盒方案，从淋巴细胞中进行 miRNA 分离程序。通过电泳筛选分离的 miRNA 的存在和质量。通过确定阈值、归一化、相关性、平均值和中位数对原始数据进行对数分析。使用不同的算法检测每个 miRNA 的靶蛋白。
在比较上皮性卵巢癌的同卵双胞胎后，发现 4 个 miRNA（miR-6131、miR-1305、miR-197-3p 和 miR-3651）上调，4 个 miRNA（miR-3135b、miR-4430、miR-664b-5p 和 miR-766-3p）下调，差异有统计学意义。
在 2549 个 miRNA 中检测到的 99 个 miRNA 可能在临床上作为新的生物学指标用于上皮性卵巢癌的诊断和随访，并进行补充研究。根据获得的数据，miRNA 表达谱在评估卵巢癌病因、BRCA1 突变状态和卵巢癌风险方面具有统计学意义。需要对 miRNA 进行验证，特别是在我们的研究中，在更大的队列中包括卵巢癌患者和健康个体中，检测到的 miRNA 与卵巢癌之间的关联。
