Prognostic Role and Potential Mechanisms of N6-methyladenosine-related Long Noncoding RNAs in Hepatocellular Carcinoma.

BACKGROUND AND AIMS

Numerous studies have explored the important role of N6-methyladenosine (mA) in cancer. Nonetheless, the interaction between mA and long noncoding RNAs (lncRNAs) is poorly investigated. Herein, we systematically analyzed the role and prognostic value of mA-related lncRNAs in hepatocellular carcinoma (HCC).

METHODS

The mA-related lncRNAs were identified based on the correlation coefficients with mA-related genes in HCC from The Cancer Genome Atlas. Subsequently, a novel risk score model was determined using the least absolute shrinkage and selection operator Cox regression analyses. Univariate and multivariate Cox analyses were used to identify independent prognostic factors for overall survival (OS) of HCC; thereafter, a prognostic nomogram was constructed.

RESULTS

A total of 259 lncRNAs showed significant correlations with mA in HCC, while 29 lncRNAs had prognostic significance. Further, six critical mA-related lncRNAs (NRAV, SNHG3, KDM4A-AS1, AC074117.1, AC025176.1, and AL031985.3) were screened out to construct a novel risk score model which classified HCC patients into high- and low-risk groups. Survival analyses revealed that patients in the high-risk group exhibited worse OS, both in the training and validation groups. The risk score was also identified as an independent prognostic factor of OS, and a nomogram was established and verified with superior prediction capacity. Besides, the risk score significantly correlated with the expression of immune checkpoint genes and immune subtypes.

CONCLUSIONS

These findings indicated the significant role of mA-related lncRNAs in HCC and the potential application of the novel risk score model for prognostic prediction.