Validation of SOCS3-DT-long non-coding RNA as potential biomarkers using well-established Human ovarian cancer cohorts

Epithelial ovarian cancer (EOC) is a lethal gynecological malignancy usually diagnosed at advanced stages due to the asymptomatic nature of the disease and the lack of early-stage biomarkers. Hence, identifying tumor biomarkers is urgently needed for the early detection of EOC. We have previously performed chromatin immunoprecipitation (ChIP) using E2F5, a biological marker highly expressed in the early stages of EOC, to identify E2F5 regulated genes with a potential to be used as an early EOC biomarker. Furthermore, gene panel exome sequencing revealed that most of the upregulated and downregulated genes regulated by E2F5 were neither mutated/deleted nor methylated in EOC. Hence, the hypothesis that alternative mechanism involving non-coding RNAs (ncRNAs) might contribute to the regulation of gene expression in EOC. Using the GDCRNA Tools (R program) and data from 376 patients in The Cancer Genome Atlas (TCGA) database, the bioinformatic analysis identified differentially expressed ncRNAs in metastatic EOC compared to primary tumors. Six lncRNAs were significantly downregulated and affected the overall survival of EOC patients. Also, Real-Time quantitative PCR (qRT-PCR) revealed differential expression of SOCS3-DT-lncRNA in EOC cell lines. In borderline cells (OSE-3), SOCS3-DT-lncRNA was downregulated than normal ovarian cells (HOSE 6-3) and upregulated in the low-grades (MCAS and A2780 Cp) cells, indicating its ability to discriminate early EOC?s stages. Furthermore, SOCS3-DT-lncRNA was recently revealed to be upregulated in low-risk breast cancer patients (BC) and was involved in regulating autophagy and serving as a prognostic marker. However, the role of SOCS3-DT-lncRNA in ovarian carcinogenesis has not yet been studied. Hence, the design of the present study to examine the potential biomarker role of SOCS3-DT-lncRNA by monitoring their differential expression in an array of human EOC samples covering normal and all the different stages (IA, IB, IC, IIB, IIC, II, IIIA, IIIB, IIIC, III, IV), using qRT-PCR. This will unravel the potential role of SOCS3-DT-lncRNA as early-stage biomarkers in EOC. Furthermore, the SOCS3-DT-lncRNA will be compared to the expression of the conventional markers (CA125, HE4), and multivariate analysis will be performed to see if the novel marker will predict EOC better than CA125, and HE4.