Exploration Of Genome-Wide Circulating Microrna In Hepatocellular Carcinoma (Hcc) - Dysregulation Of Mir-483-5p And Mir-150 As Diagnostic Marker.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC The incidence of hepatocellular carcinoma (HCC) has doubled over the past 20 years in the United States (US). HCC prognosis is poor if not diagnosed and treated at an early stage. MicroRNAs (miRNAs) are a class of small non-coding RNAs that control gene expression by inhibiting translation or inducing cleavage of target messenger RNAs (mRNAs). miRNAs can regulate diverse biological processes including DNA repair, apoptosis, cell proliferation, differentiation and immune function. Circulating miRNAs in cell-free plasma/serum samples have been consistently observed to have high stability and resistance to storage/handling, suggesting their potential use as diagnostic biomarkers. We conducted a two-phase epidemiological case-control study to test the hypothesis that genome-wide dysregulation of circulating miRNAs differentiate HCC cases from controls. A total of 69 HCC patients and 69 controls were recruited and matched on age, gender and ethnicity. Taqman low density arrays were used to examine genome-wide miRNA expression, and quantitative RT-PCR was used to validate promising candidates. Sixty-six miRNAs were found to be significantly over-expressed in plasma of HCC cases compared to controls after adjusting for false discovery rate (p<0.05). A volcano plot indicated that 7 miRNAs had over 2-fold case-control differences with p<0.01. Four significant miRNAs (miR-150, miR-30c, miR-483-5p and miR-520b) detectable in all samples with varied expression levels were further validated in an expanded case-control study. MiR-483-5p was statistically significantly over-expressed in HCC cases compared with controls (3.25 vs. 0.54, p<0.0001). MiR-150 was up-regulated in HCC, but the difference was not significant (5.66 vs. 5.29). The combination of plasma levels of miR-483-5p and miR-150 can significantly differentiate HCC cases from controls with an AUC of 0.850 (p<0.0001). The sensitivity and specificity were, respectively, 63.8% and 85.5%. These preliminary data indicated the importance of dysregulated circulating miRNAs in hepatocarcinogenesis, and suggesting the possibility of using miR-483-5p and miR-150 as diagnostic biomarkers. Large prospective studies are necessary to replicate the current findings, and evaluate the panel of circulating miRNAs in improving early diagnosis of HCC. Citation Format: Jing Shen, Antai Wang, Qiao Wang, Irina Gurvich, Abby B. Siegel, Helen Remotti, Regina M. Santella. Exploration of genome-wide circulating microRNA in hepatocellular carcinoma (HCC) - dysregulation of miR-483-5p and miR-150 as diagnostic marker. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-25. doi:10.1158/1538-7445.AM2013-LB-25