Bioinformatic analysis of the prognostic value of the lncRNAs encoding snoRNAs in hepatocellular carcinoma.

Some lncRNAs can encode small nucleolar RNAs (snoRNAs), called small nucleolar RNA host genes (SNHGs), which exert diverse regulatory effects on cellular processes. In this study, using RNA-seq and survival data in the Cancer Genome Atlas (TCGA)-Liver Hepatocellular Carcinoma (LIHC), we examined the expression profile of some SNHG genes and explored their prognostic value in hepatocellular carcinoma (HCC). Level-3 RNA-sequencing data, the clinicopathological and survival data of patients with primary HCC were downloaded from the UCSC Xena browser (https://xenabrowser.net/), for a secondary analysis. Results showed that SNHG1, GAS5, SNHG3-7 and SNHG10-12 were significantly upregulated in HCC tissues (N = 49) compared with adjacent normal tissues (N = 49). After adjustment for confounding factors, the multivariate analysis confirmed that increased SNHG4 expression was independently associated with shorter OS (HR: 1.319, 95%CI: 1.131-1.537, P < 0.001), while increased GAS5 expression was an independent predictor of shorter RFS (HR: 1.287, 95% CI: 1.027-1.612, P = 0.028). Using the methylation data obtained from the Infinium HumanMethylation450 BeadChip, we found that SNHG4 expression was not likely to be modulated by methylation in HCC. In comparison, the methylation status of 5 CpG sites (cg07177756, cg17025683, cg16290996, cg03044573 and cg06644515) showed a moderately negative correlation (Pearson's r = -0.54, P < 0.001) with GAS5 expression. Based on these findings, we infer that SNHG4 and GAS5 might be valuable prognostic markers in HCC. DNA hypomethylation might play an important role in elevated GAS5 transcription in HCC.