Abstract
BackgroundOvarian 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.MethodsThe 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.ResultsAfter 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.ConclusionsThe 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.
Highlights
Ovarian cancer is the second most common gynecologic cancer with high mortality rate and generally diagnosed in advanced stages
There is a need for validation of the miRNAs which were 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
After investigation of ovarian cancer monozygotic discordant twins and their healthy family members 99 miRNAs were identified for the first time. miRNAs detected in different cancer types in the literature were parallel with the miRNA expression levels in our study
Summary
Ovarian cancer is the second most common gynecologic cancer with high mortality rate and generally diagnosed in advanced stages. The most common of this indicators are the cancer antigen-125 (CA125) and cancer antigen-15-3 (CA-15-3) These biological indicators can be used in the follow-up of the treatment response in the diagnosed patients but cannot be used in the early diagnosis and in differentiation of the malignant disease [19]. In order to clearly define the role of miRNAs in the pathogenesis of ovarian cancer, we planned to investigate the BRCA mutant monozygotic twins with the same genetic profile but with discordant for ovarian malignant transformation. 2549 miRNAs, which are thought to have the potential biological indicator role, were studied from blood samples of both discordant monozygotic twins and BRCA wild type healthy siblings
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