The survival prediction analysis and preliminary study of the biological function of YEATS2 in hepatocellular carcinoma

Purpose: Our study aims to develop and validate a novel molecular marker for the prognosis and diagnosis of hepatocellular carcinoma (HCC) MATERIALS & METHODS: We retrospectively analyzed mRNA expression profile and clinicopathological data of HCC patients fetched from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and The International Cancer Genome Consortium (ICGC) datasets. Univariate Cox regression analysis was performed to collect differentially expressed mRNA (DEmRNAs) from HCC and non-tumor tissues, and YEATS2, a prognostic marker, was identified by further analysis. ROC curve, survival analysis and multivariate Cox regression analysis as well as nomograms were used to evaluate the prognosis of this gene. Finally, the biological function of this gene was preliminarily discussed by using single gene Gene Set Enrichment Analysis (GSEA), and the YEATS2 overexpression and knockdown hepatoma cell line was used to verify the results in vitro and in vivo.

Results: Based on the clinical information of HCC in TCGA, GEO and ICGC databases, the gene YEATS2 with significant differences from HCC was identified. There was a statistical difference in the survival prognosis between the two databases and the ROC curve showed that the survival of HCC in both TCGA, GSE14520 and ICGC groups had a satisfactory predictive effect. Univariate and multivariate Cox regression analysis showed that YEATS2 was an independent prognostic factor for HCC, and Nomograms, which combined this prognostic feature with significant clinical features, provided an important reference for the clinical prognostic diagnosis of HCC. Next, we constructed overexpression and knockdown YEATS2 cell line in Hep3B and LM3 cells, and further proved that overexpression YEATS2 promote the proliferation and migration of HCC cells by CCK8, colony formation experiment, and transwell assays, and knockdown YEATS2 inhibited the proliferation and migration of HCC cells by CCK8, colony formation experiment, and transwell assays. Finally, the biological function of YEATS2 was preliminarily explored through GSEA analysis of a single gene, and it was found that it was significantly correlated with cell cycle and DNA repair, which provided us with ideas for further analysis. Furthermore, the knockdown of YEATS2 promoted radiation-induced DNA damage, enhanced radiosensitivity, and ultimately inhibited the proliferation of hepatocellular carcinoma cells in vitro and in vivo.

Conclusions: Our study identified a promising prognostic marker for hepatocellular carcinoma that is useful for clinical decision-making and individualized treatment.