Risk Scoring System based on lncRNA Expression for Predicting Survival in Hepatocellular Carcinoma with Cirrhosis.

Jiaxiang Ye,Yue Luo,Jiazhang Wei,Xiaoling Luo,Hongmei Liu,Haixia Li,Jinyan Zhang

doi:10.31557/apjcp.2020.21.6.1787

Abstract

Objective:This study aims to explore the roles of long non-coding RNAs (lncRNAs) for predicting survival in hepatocellular carcinoma (HCC) patients with cirrhosis. Methods:A set of lncRNAs differentially expressed between HCC patients with or without cirrhosis was identified using expression profiles of The Cancer Genome Atlas database, and these lncRNAs were screened for their risk scoring system to predict recurrence-free survival (RFS) or overall survival (OS). Predictive ability of risk scoring systems was confirmed using uni- and multivariate Cox analyses while adjusting for clinical features. Predictive lncRNAs were analyzed by functional enrichment analysis. Results:Our screen identified 22 lncRNAs that were upregulated in the presence of cirrhosis and 59 that were downregulated. To predict OS of HCC patients with cirrhosis, a risk scoring system was developed with four lncRNAs (LINC02086, LINC00880, LINC01549 and AC136475.3); to predict RFS in these patients, the risk scoring system contained five lncRNAs (SH3RF3-AS1, AC104117.3, AC136475.3, LINC00239 and MRPL23-AS1). All risk scoring systems were associated with an area under the receiver operating characteristic curve > 0.7. Based on uni- and multivariate Cox analyses, the risk scoring system could serve as a significant independent predictor for OS in HCC patients with cirrhosis. Functional enrichment analysis suggested that the lncRNAs in the risk scoring systems are involved primarily in the pathway of Wnt signal and cytokine-cytokine receptor interaction. Conclusion:Risk scoring systems based on lncRNAs can effectively predict OS of HCC patients with cirrhosis. The system should be further developed and validated in larger, preferably multi-site patient populations.

Highlights

Liver cancer remains the sixth most frequent cancer globally, with approximately 841,000 new diagnosed cases and 782,000 deaths annually
LncRNAs differentially expressed in the presence or absence of cirrhosis in hepatocellular carcinoma (HCC) patients Our analysis included the long non-coding RNAs (lncRNAs) expression profiles in 77 HCC patients with cirrhosis and 130 HCC without cirrhosis obtained from the The Cancer Genome Atlas (TCGA) database
After adjusting for other clinical variables, uni- and/ or multivariate Cox analyses showed the lncRNA-based scoring system to be significantly associated with overall survival (OS) of HCC patients with cirrhosis, suggesting the lncRNA-based scoring system can serve as a significant independent predictor

Summary

Introduction

Liver cancer remains the sixth most frequent cancer globally, with approximately 841,000 new diagnosed cases and 782,000 deaths annually. Hepatocellular carcinoma (HCC) is the most frequent common liver cancer, accounting for 75–85% of liver cancers (Bray et al, 2018; Forner et al, 2018; Kulik and El-Serag, 2019). Despite significant improvements in diagnosing and treating HCC, its heterogeneity means that it continues to be associated with relatively low rates of recurrence-free survival (RFS) and overall survival (OS) (Bruix et al, 2014; Fong and Tanabe, 2014). No biomarkers have proven effective for predicting prognosis, reflecting the complicated nature of the disease. Further efforts are needed to identify biomarkers that can predict prognosis and guide treatment. Long non-coding RNAs (lncRNAs), located in the cytoplasm and nucleus of eukaryotic cells, are non-coding

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Conclusion