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

Fawzy Roshdy,Adel A Mousa,Mohamed El Talkawy,Ola Mahmode,Eman El-Ahwany,Mohamed M S Farag,Faiza Essawy

doi:10.1186/s43042-020-0048-8

Abstract

BackgroundLong 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.ResultsLncRNAs (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.ConclusionThese 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.

Highlights

Long non-coding RNAs homeobox (Hox) transcript antisense intergenic RNA (HOTAIR) and homeobox A (HOXA) transcript at the distal tip (HOTTIP) have been suggested to be implicated in liver cancer tumorigenesis and progression; little is known about the role of the plasma Hox transcript antisense intergenic RNA (HOTAIR) and HOXA transcript at the distal tip (HOTTIP) in liver cancer diagnosis and prognosis
Depending on the fold change low, the fold change results showed that the gene expressions of HOTAIR and HOTTIP constantly upregulated in the studied groups (Table 3)
All parameters are represented as median with interquartile range (25%–75%) of the fold change of the studied groups, the data were analyzed by Mann-Whitney U test p value bearing (a) initial is significantly different comparing with control group p value bearing (b) initial is significantly different comparing with hepatitis C virus (HCV) group p value bearing (c) initial is significantly different comparing with cirrhotic group p value bearing (#) initial is significantly different comparing with chronic liver disease (CLD) group 1 initialp value < 0.05 is significant, 2 initial p value < 0.01 is highly significant development of tumors has been revealed and can be used as a promising biomarker to diagnose and monitor tumors, and Long non-coding RNAs (lncRNAs) could be collected from body fluids and tumor tissues [41]

Summary

Introduction

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; 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. HCV infection is a major cause of CLD, which can progress to liver fibrosis, cirrhosis and even HCC [1]. LncRNAs account for a large portion of the non-coding transcripts. They comprise of in excess of 200 nucleotides and have no or restricted protein-coding potential. A solid affiliation has been found between deregulated lncRNA articulation and the improvement of maladies

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