Long non-coding RNA HOTAIR and HOTTIP as potential biomarkers for hepatitis C virus genotype 4-induced hepatocellular carcinoma

Abstract

Background: Long non-coding RNAs (lncRNAs) homeobox (Hox) transcript antisense intergenic RNA (HOTAIR) and HOXA transcript at the distal tip (HOTTIP) have been suggested to be implicated in liver cancer tumorigenesis and progression; however, little is known about the role of the plasma HOTAIR and HOTTIP in liver cancer diagnosis and prognosis. The current study aimed at measuring the plasma levels of long non-coding RNAs (HOTAIR and HOTTIP) expression in chronic liver disease (CLD) due to HCV genotype 4 infection with/without cirrhosis and HCC patients in an attempt to evaluate the potential benefits of these new circulating as non-invasive diagnostic biomarkers and a novel therapeutic strategy for liver cirrhosis and carcinogenesis of Egyptian patients. Hundred subjects were included in this study, divided into two groups; group I (50 patients) were classified into subgroup Ia (CLD without cirrhosis, n = 25) and subgroup Ib (CLD with cirrhosis, n = 25), group II (CLD patients with HCC, n = 25), and control (healthy volunteer, n = 25). The expression of lncRNAs (HOTAIR and HOTTIP) genes was analyzed by real-time PCR. Results: LncRNAs (HOTAIR and HOTTIP) showed upregulation in all diseased groups, which was in consistent with the progression of the disease toward the HCC stage. In addition, HOTAIR and HOTTIP showed a diagnostic ability to discriminate between cases of cirrhosis and HCC compared with healthy control (p < 0.001), while HOTAIR and HOTTIP did not show a discrimination significant differences between cirrhotic cases and non-cirrhotic cases. By using receiver operating characteristic curve (ROC) analysis, it was found that LncRNAs (HOTAIR and HOTTIP) could diagnose liver cancer with 64.0% sensitivity and 86.0% specificity and 48.0% sensitivity and 88.0% specificity. Furthermore, both genes can be considered as the predictor and prognostic parameters for cirrhosis (OR = 1.111, p = 0.05) and (OR = 1.07, p = 0.05) respectively, and HCC (OR = 1.047, p = 0.01) and (OR = 1.05, p = 0.003). The increased HOTAIR and HOTTIP expression were associated with advanced tumor stages and higher grades. Conclusion: These results strongly prompt us that HOTAIR and HOTTIP genes can be used as non-invasive prognostic biomarkers and new therapeutic targets for HCV genotype 4-induced HCC.