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

Abstract

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.