Bioinformatics analysis and experimental validation of cystathionine-gamma-lyase as a potential prognosis biomarker in hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis and high mortality worldwide.Although cystathionine-gamma-lyase (CSE) plays an important role in the development of multiple tumors, the clinical implication and potential mechanisms of CSE in HCC development remain elusive.Methods: In our study, the CSE expression in HCC was analyzed in Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets and further confirmed by RT-qPCR and immunohistochemistry assays in HCC samples.Furthermore, the associations between CSE expression and HCC malignancy as well as survival were analyzed in GSE14520 and validated in HCC patients.Finally, the biological functions of CSE in HCC cells was assessed by CCK-8, flow cytometry and Western blotting.Results: Lower transcriptional and proteomic CSE expressions were found in HCC tissues in contrast to adjacent normal tissues.Decreased CSE mRNA expression was significantly associated with advanced clinicopathological features and poor outcomes in HCC patients from public database and our cohort.Following univariate and multivariate analyses of GSE14520 data showed that CSE expression was an independent prognostic indicator for the overall survival (OS) and recurrence-free survival (RFS) of HCC patients.In vitro experiments further explained that CSE might trigger HCC cell apoptosis by H 2 S. Conclusion: In summary, the present study identified the relationship between CSE expression and HCC malignancy as well as OS and RFS, indicating that CSE might be a potential prognostic biomarker and a novel therapeutic target for HCC.