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

Purpose: Hepatocellular carcinoma (HCC) is a common malignant tumor with 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: The CSE expression in HCC was analyzed in GEO and TCGA datasets and verified in 45 HCC patients samples by RT-qPCR and immunohistochemistry assays. Furthermore, the associations between CSE expression and HCC malignancy as well as survival were analyzed in GSE14520 and validated in HCC patients. Cox proportional hazard model was used to identify prognostic factors for overall survival(OS) and recurrence-free survival(RFS) in GSE14520. CCK-8 and flow cytometry were used to assess the biological functions of CSE in HCC cells, including cell proliferation and apoptosis. 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 survival 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 OS and RFS of HCC patients. Notably, inhibition of CSE with PPG, facilitated proliferation and suppressed apoptosis in HCC cells via H 2 S. Conclusion: In summary, the present study identified the relationship between CSE expression and HCC malignancy as well as OS and RFS, suggestting that CSE might be a potential prognostic biomarker and a novel therapeutic target in cancer therapy.