Assessment of lncRNA GAS5, lncRNA HEIH, lncRNA BISPR and its mRNA BST2 as serum innovative non-invasive biomarkers: Recent insights into Egyptian patients with hepatitis C virus type 4

Abstract

Background: Hepatitis C virus (HCV) infection and its consequent complications are undeniably a public health burden worldwide, particularly in Egypt. Emerging evidence suggests that many lncRNAs have relevant roles in viral infections and antiviral responses.

Aim: To investigate the expression profiles of circulating lncRNAGAS5, lncRNAHEIH, lncRNABISPR and mRNABST2 in naïve, treated and relapsed HCV Egyptian patients, to elucidate relation to HCV infection and their efficacy as innovative biomarkers for the diagnosis and prognosis of HCV GT4.

Methods: One hundred and thirty HCV-infected Egyptian patients and 20 healthy controls were included in this study. Serum lncRNAs and mRNABST2 were measured using quantitative real-time polymerase chain reaction (qRT-PCR).

Results: Our results indicated that serum lncRNAGAS5 and LncRNABISPR were upregulated, whereas mRNA BST2 and LncRNA HEIH were downregulated in naïve patients. In contrast, HCV patients treated with sofosbuvir and simeprevir; with sofosbuvir and daclatasvir; or with sofosbuvir, daclatasvir and ribavirin exhibited lower levels of lncRNAGAS5 and lncRNABISPR with higher mRNABST2 compared to naïve patients. Notably, patients relapsed from sofosbuvir and simeprevir showed higher levels of these lncRNAs with lower mRNABST2 compared to treated patients. LncRNAGAS5 and lncRNABISPR were positively correlated with viral load and ALT at P < 0.001, whereas mRNABST2 was negatively correlated with viral load at P < 0.001 and ALT at P < 0.05. Interestingly, a significant positive correlation between lncRNA HEIH and AFP was observed at P < 0.001.

Conclusion: Differential expression of these RNAs suggests their involvement in HCV pathogenesis or antiviral response and highlights their promising roles in diagnosis and prognosis of HCV.

Keywords: Biomarkers; Hepatitis C; lncRNA BISPR; lncRNA GAS5; lncRNA HEIH; mRNA BST2.

Figure 1

Serum expression levels of lncRNAs and mRNA in healthy controls, hepatitis C virus naïve patients and hepatitis C virus treated patients with different treatment regimens. A: LncRNA GAS5; B: LncRNA BISPR; C: LncRNA HEIH; D: mRNA BST2. ^bP < 0.01, vs control group; ^dP < 0.01, vs naïve group; Data were analyzed by On e-way ANOVA test followed by Tukey HSD multiple comparison test.

Figure 2

Serum LncRNAs and mRNA as diagnostic biomarker for naïve patients. ROC curve analysis for lncRNA Gas 5 (AUC = 0.88) (A), BISPR (AUC = 0.82) (B), HEIH (AUC = 0.88) (C) and mRNA BST2 (AUC = 0.85) (D) as diagnostic biomarkers discriminating naïve patients from healthy controls.

Figure 3

Serum LncRNAs and mRNA as prognostic biomarker for hepatitis C virus treated patients with different treatment reginens. ROC curve analysis for SOF + SIM (A), SOF + DAC (B), and SOF + DAC + RBV (C) as prognostic biomarkers discriminate treated from naïve patients. 1st LncRNA gas 5; 2nd LncRNA BISPR; 3rd LncRNA HEIH; 4th mRNA BST2.

Figure 4

Differential expression of serum lncRNAs and mRNA levels in hepatitis C virus relapsed, naïve and SOF + SIM treated hepatitis C virus patients. ^aP < 0.05, ^bP < 0.01, vs naïve group; ^dP < 0.01, vs SOF + SIM group.

Figure 5

Serum LncRNAs and mRNA as prognostic biomarker for relapsed patients. ROC curve analysis for lncRNA Gas 5 (AUC = 0.91) (A), BISPR (AUC = 0.84) (B), HEIH (AUC = 0.95) (C) and mRNA BST2 (AUC = 0.86) (D) as prognostic biomarkers discriminating relapsed from treated from SOF + SIM patients.