Abstract 3969: Hepatic microRNA as biomarker for detection of hepatocellular carcinoma in high-risk chronic Hepatitis B patients

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Abstract a) Absence of pathognomonic symptoms in patients with early phase of hepatocellular carcinoma (HCC) often leads to untreatable disease when diagnosed. Alpha-fetoprotein (AFP) with radiological images is the only potential HCC diagnosis option while disease prognosis remains dismal mandating necessity of biomarker identification with diagnostic, prognostic potentials as well as ability to assist in therapy. Thus this study aimed to identify non-invasive biomarker correlated with HCC pathogenesis by analyzing deregulated miRNAs in premalignant liver cirrhosis (LC) and in HCC. b) Among 148 study subjects, 117 were chronic Hepatitis B virus (HBV) (NAsymptomatic- control = 28, NLC = 30, NHCC = 59), 14 chronic Hepatitis C virus (HCV) infected (NLC = 7, NHCC = 7) and 17 were uninfected control. Differential expression profiling of miRNAs in each of 4 HBV infected LC and HCC tissues were performed by comparing with 8 asymptomatic controls using microarray and validated by qRT-PCR. R packages were used to determine area under receiver operating characteristics (AUROC) curve and other statistical analysis. Different softwares were used for prediction of target pathways associated with HCC development. c) Microarray analysis leads to identification of significantly altered [> or < 1.5 fold, p value <0.05] 42 miRNAs in HCC and 65 in LC. Ten common altered miRNAs with high signal intensity were validated in both HBV (10 from each stage) and HCV (7 from each stage) infected tissues and only six miRNAs were successfully validated by qRT-PCR. Subsequently, expression of only two miRNAs, miR-126 and miR142-3p were found significantly higher in HCC plasma compared to asymptomatic control (p<0.05). But expressions of both miRNAs were similar between LC and HCC+LC plasma while it was significantly higher in HCC-LC (p<0.05). Further, AUROC value to discriminate HCC from non-HCC was found higher for miR-126, 0.83 [95% CI (0.74-0.91), p<0.05] with 80% sensitivity and 81% specificity than AFP, which was 0.77 [95% CI (0.68-0.86)] with 72% sensitivity and 87% specificity, while combination achieved highest AUROC of 0.94 [95% CI (0.9-0.99)] with 89% sensitivity and 93% specificity. Moreover, high expression of miR-126 in sample with low AFP [<250ng/ml in 32.6% of HCC (16/49)] and AUROC of 0.896 [95% CI (0.78-1)] with 88% sensitivity and 81% specificity implicates the diagnostic importance of miR-126. To gain insight into the pathophysiological role of miR-126 in HCC development different target prediction programs were used and correlated with gene expression data of HCC from “Oncomine” followed by KEGG pathway analysis which revealed target genes from MAPK, cytokine-cytokine receptor interaction and metabolic pathways. d) In conclusion, combination of miR-126 with AFP may be a better predictor of HCC in high-risk chronic hepatitis patients and miR-126 alone can show better performance in detection of HCC with low AFP. Citation Format: Amit Ghosh, Alip Ghosh, Somenath Datta, Debanjali Dasgupta, Soumyajit Das, Sukanta Ray, Subash Gupta, Simanti Datta, Abhijit Chowdhury, Saroj Kant Mohapatra, Soma Banerjee. Hepatic microRNA as biomarker for detection of hepatocellular carcinoma in high-risk chronic Hepatitis B patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3969. doi:10.1158/1538-7445.AM2015-3969