Integrated Analysis of N1-Methyladenosine Methylation Regulators-Related lncRNAs in Hepatocellular Carcinoma

SIMPLE SUMMARY: The relationship between m1A-related lncRNAs and HCC is still unclear. In this study, five m1A-related lncRNAs (AL031985.3, NRAV, WAC-AS1, AC026412.3, and AC099850.4) were identified and used to develop a prognostic signature. The prognostic signature was an independent risk factor related to OS in HCC patients. Synergistic effects on patient survival were observed after combining with TP53 or TMB. In addition, we also screened small molecules which could be potential drugs for HCC patients. Our results suggested that five m1A-related lncRNAs generated a prognostic signature that could be a promising prognostic prediction approach and therapeutic response assessment tool for HCC patients. To the best of our knowledge, this is the first study of m1A-related lncRNAs in HCC. ABSTRACT: N1-methyladenosine (m1A) and long non-coding RNAs (lncRNAs) play significant roles in tumor progression in hepatocellular carcinoma (HCC). However, their association with HCC is still unclear. In this study, lncRNAs related to m1A were extracted from the mRNA expression matrix in The Cancer Genome Atlas (TCGA) database. Five m1A-related lncRNAs (AL031985.3, NRAV, WAC-AS1, AC026412.3, and AC099850.4) were identified based on lasso Cox regression and they generated a prognostic signature of HCC. The prognostic signature was identified as an independent prognosis factor in HCC patients. Moreover, the prognostic signature achieved better performance than TP53 mutation status or tumor mutational burden (TMB) scores in the stratification of patient survival. The immune landscape indicated that most immune checkpoint genes and immune cells were distributed differently between both risk groups. A higher IC(50) of chemotherapeutics (sorafenib, nilotinib, sunitinib, and gefitinib) was observed in the high-risk group, and a lower IC(50) of gemcitabine in the low-risk group, suggesting the potential of the prognostic signature in chemosensitivity. In addition, fifty-five potential small molecular drugs were found based on drug sensitivity and NRAV expression. Together, five m1A-related lncRNAs generated a prognostic signature that could be a promising prognostic prediction approach and therapeutic response assessment tool for HCC patients.