lncRNAs as prognostic molecular biomarkers in hepatocellular carcinoma: a systematic review and meta-analysis

Abstract

The latest studies have shown that long non-coding RNAs (lncRNAs) may be considered markers as their expression levels were abnormal in cancer and can be used as a molecular biomarker for the potential assessment of cancer prognosis. In this study, we aimed to assess the prognostic value of lncRNA as marker of patients with hepatocellular carcinoma. We performed a detailed search of the PubMed and Embase databases for articles on the prognostic value of various lncRNAs in HCC. We then carefully extracted the relevant data from the articles, and we used the meta-analysis method to analyze these results; heterogeneity and publication bias were also evaluated. With 40 associative studies included, we found that high expression of 27 types of lncRNA was associated with a poor prognosis in HCC patients, and low expression of 18 types of lncRNAs was associated with a worse prognosis. Patients with higher lncRNA expression had significantly poor overall survival (OS; pooled HR, 1.25; 95% confidence interval [CI], 1.03-1.52) as well as significantly poor recurrence-free survival (RFS; pooled HR, 1.66; 95% CI, 1.26-2.17). Overexpression of lncRNAs may not meaningfully predict disease-free survival (DFS; pooled HR, 1.04; 95% CI, 0.52-2.07; p = 0.91). Our meta-analysis demonstrated that lncRNAs may serve as predictive biomarkers for cancer prognosis.

Keywords: hepatocellular carcinoma (HCC); lncRNA; meta-analysis; prognostic; survival.

Figure 1. Flow diagram of the study selection process

A final total of 40 articles were included for meta-analysis.

Figure 2. The histogram for hazard ratio (HR) and 95% confidence interval (95%CI) values of each lncRNA affected the survival rate of HCC

(A) Overall survival (OS). (B) Disease-free survival (DFS). (C) Recurrence-free survival (RFS). (Take the 26TUSC7 for example, it contains two parts. The number of 26 represents the serial number among the 40 stuies, and the TUSC7 stand for the lncRNAs’ name).

Figure 3. Forest plots of the studies to assess the pooled hazard ratio (HR) and 95% confidence interval (95%CI) values of lncRNAs

(A) Overall survival (OS). (B) Disease-free survival (DFS). (C) Recurrence-free survival (RFS).

Figure 4. Sensitivity analysis to evaluate the stability and reliability of meta-analysis results

There was no change in the pooled HR results after excluding any research data of one study.

Figure 5. Use of Begg's funnel plot to evaluate publication bias of the included studies

There was no significant publication bias for all the included studies. (A) Overall survival (OS). (B) Disease-free survival (DFS). (C) Recurrence-free survival (RFS).