Use of 6 m6A-relevant lncRNA genes as prognostic markers of primary liver hepatocellular carcinoma based on TCGA database

Background: Hepatocellular carcinoma (HCC) is diagnosed at the middle and advanced stages, negating radical treatment. Identifying specific and effective prognostic HCC biomarkers is important and can facilitate the discovery of potential therapeutic targets. N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) are associated with the development of multiple tumors. The role of m6A-relevant lncRNAs in the initiation and progression of HCC is unclear. The aim of the present study was to investigate the expression of m6A-relevant lncRNAs in HCC and to identify new prognostic markers of the disease.

Methods: Gene expression and clinical data were retrieved from The Cancer Genome Atlas database. m6A-relevant lncRNAs were identified by co-expression analysis and were screened by univariate Cox regression analysis. Different HCC patient clusters were established via consensus clustering. Gene set enrichment analysis (GSEA) was used to determine the cluster enrichment pathways. A risk score model was constructed, and Kaplan-Meier analysis of the overall survival (OS) between cluster 1 (high risk) and cluster 2 (low risk) was performed. Relationships between the clusters, risk scores, and clinicopathological characteristics were clarified.

Results: Of the 1,852 m6A-relevant lncRNAs identified, 68 had prognostic relevance. The pathological grade, American Joint Committee on Cancer stage, and T stage of cluster 1 were significantly more advanced than those of cluster 2. Based on GSEA, mitotic spindle, G2M_CHECKPOINT, glycolysis, the phosphoinositide 3-kinase (PI3K) protein kinase B (AKT) mammalian target of rapamycin (mTOR) pathway, and DNA repair were more enriched in cluster 1. Six key m6A-relevant lncRNAs were selected to build a risk score model predicting the prognosis of HCC. The OS of patients in the high-risk group was shorter than that of patients in the low-risk group. Risk score was an independent prognostic factor of HCC patients.

Conclusions: The findings indicated that m6A-relevant lncRNAs may be important in the progression of HCC. The risk score model based on the 6 key m6A-relevant lncRNAs can accurately predict the prognosis of patients with HCC.