Alcohol and hepatitis virus-dysregulated lncRNAs as potential biomarkers for hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths because of frequent late detection and poor therapeutic outcomes, necessitating the need to identify effective biomarkers for early diagnosis and new therapeutic targets for effective treatment. Long noncoding RNAs (lncRNAs) have emerged as promising molecular markers for diagnosis and treatment. Through analysis of patient samples from The Cancer Genome Atlas database, we identified putative lncRNAs dysregulated in HCC and by its risk factors, hepatitis infection and alcohol consumption. We identified 184 lncRNAs dysregulated in HCC tumors versus paired normal samples, 53 lncRNAs dysregulated in alcohol-drinking patients with hepatitis B, and 5, 456 lncRNAs dysregulated in patients with hepatitis infection. A panel of these candidate lncRNAs’ expressions correlated significantly with patient survival, clinical variables, and known genomic alteration in HCC. Two most significantly dysregulated lncRNAs in our computational analysis, lnc-CFP-1:1 and lnc-CD164L2-1:1, were validated in vitro to be dysregulated by alcohol. Our findings suggest that lncRNAs dysregulated by different etiologies of HCC serve as potential disease markers and can be further investigated to develop personalized prevention, diagnosis, and treatment strategies.