Evaluation of Long Non-Coding RNA Expression in Liver Cirrhosis and Hepatocellular Carcinoma Secondary to Liver Cirrhosis

Project no. 26346 · Status: Kapanmış (Yayın bekleniyor) · 2022

Summary

Introduction and Aim: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is associated with a poor prognosis. In high-risk populations such as those with liver cirrhosis, early detection of HCC and the discovery of novel therapeutic targets are of great importance. A better understanding of epigenetic mechanisms in HCC may facilitate such progress. In this study, the expression profiles of 84 predefined long non-coding RNAs (lncRNAs) were analyzed in patients with HCC, cirrhosis, and healthy controls to explore potential roles of lncRNAs in cirrhosis and in HCC arising on a cirrhotic background.Materials and Methods: This observational, cross-sectional case–control study included 20 patients with HCC, 18 with liver cirrhosis, and 20 healthy volunteers who presented to the Gastroenterology Department of Ege University between 2023 and 2024. Peripheral blood samples were collected from all participants, and lncRNA expression was analyzed using a commercial qPCR array panel containing a set of predefined lncRNA targets.Results: The median age of all participants was 61 years. Median ages were 67, 62, and 55 years in the HCC, cirrhosis, and control groups, respectively (p < 0.001). Of all participants, 39 (67.2%) were male and 19 (32.8%) were female. The male-to-female ratio was 19/1 in the HCC group, 10/8 in the cirrhosis group, and 10/10 in the control group (p = 0.004). During follow-up, 23 patients (60.5%) died 18 (90%) in the HCC group and 5 (27.8%) in the cirrhosis group (p < 0.001). Comparative analysis of lncRNA expression among groups revealed that the following lncRNAs showed statistically significant differences between HCC and cirrhosis: IGF2AS, NRON, p21, Alpha-250, KRASP1, UCA1, HOXA-AS3, antiPeg11, BC200, 7SK, H19-upstream, HAR1A, HOTTIP, HOXA11-AS, SRA, Nespas, DIO3OS, Kcnq1ot1, MEG3, NDM29, Alpha-280, Jpx, E2F4-antisense, SNHG1, H19-antisense, EMX2OS, ANRIL, Air, SNHG5, PSF-inhibiting, Gomafu, MEG9, and SNHG3. All of these lncRNAs were expressed at lower levels in the HCC group than in the cirrhosis group. Receiver operating characteristic (ROC) analysis identified lncRNAs with the highest diagnostic performance (AUC values) in differentiating HCC from cirrhosis as follows: IGF2AS (0.99), UCA1 (0.89), Alpha-250 (0.89), NRON (0.88), KRASP1 (0.87), p21 (0.87), HOXA-AS3 (0.86), antiPeg11 (0.86), BC200 (0.86), 7SK (0.84), HAR1A (0.83), H19-upstream (0.83), HOXA11-AS (0.82), HOTTIP (0.82), Kcnq1ot1 (0.80), and MEG3 (0.80).Conclusion: lncRNAs that exhibited markedly decreased plasma expression in HCC compared with cirrhosis—and demonstrated the highest diagnostic potential in distinguishing HCC from cirrhosis—were IGF2AS, UCA1, Alpha-250, NRON, KRASP1, p21, HOXA-AS3, antiPeg11, and BC200. These findings suggest that circulating lncRNAs may serve as promising non-invasive biomarkers for the early detection of HCC in patients with liver cirrhosis.

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