Construction of a m5C-related long non-coding RNA signature for the prognosis of hepatocellular carcinoma

Hum Cell. 2023 Mar;36(2):712-724. doi: 10.1007/s13577-022-00845-8. Epub 2022 Dec 15.

Abstract

RNA modification serves as a kind of posttranscriptional modification. Besides N6-methyladenosine (m6A), 5-methylcytosine(m5C) is also an important RNA modification. Long non-coding RNAs (lncRNAs) play an important role in tumor progression. Thus, we performed bioinformatic analysis to establish a m5C-related lncRNA signature(m5ClncSig) for hepatocellular carcinoma (HCC). The RNA sequencing data and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Pearson correlation coefficient analysis was applied to conduct m5C-related genes and m5C-related lncRNAs co-expressing network. Univariate Cox regression was used to screen the m5C-related lncRNAs with prognosis value. LASSO regression was applied to establish m5ClncSig. Functional analysis including KEGG and GO were performed. The relation between m5ClncSig and immunity was assessed by CIBERSORT and ESTIMATE. RP11-498C9.15 was selected for in vitro validation. A m5ClncSig was established containing 8 lncRNAs with significantly prognosis value. According to risk score calculated by m5ClncSig, high-risk group had worse clinical outcomes than low-risk group. The risk score was validated as an independent prognosis factor. Moreover, the abundances of 11 types of immune cells were significantly different between high-risk group and low-risk group while 8 immune-related genes expressed differently between these two groups. RP11-498C9.15 was validated as a risk factor in HCC progression.

Keywords: HCC; Immunity; Prognosis; lncRNA; m5C DNA methylation.

MeSH terms

  • Carcinoma, Hepatocellular*
  • Humans
  • Liver Neoplasms*
  • RNA, Long Noncoding*
  • Risk Factors

Substances

  • RNA, Long Noncoding