Abstract
Objective: To study the relationship between cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH) genes-related signaling pathways in liver cancer cells. Methods: We conducted a correlation analysis between the clinical features of CBS and CTH gene expression by mining the GEO (Gene Expression Omnibus) and TCGA (The Cancer Genome Atlas) databases of liver cancer. Additionally, liver cancer cell lines were verified by immunoblotting. Results: CBS and CTH expressions were significantly lower in tumors than in non-tumors (P < 0.05). COX regression result showed that CBS was an independent risk factor for the poor prognosis of liver cancer cells (HR=0.65, P = 0.02). A univariate logistic regression analysis was performed on the different tumor stages focusing on the CBS gene, which showed that TNM stage II verses I (P = 0.01, OR=0.50), stage III verses I (P = 0.03, OR=0.56), T stage T2 verses T1 (P < 0.01, OR=0.43), and T3 stage verses T1 (P = 0.02, OR=0.54) were significantly lower in liver cancer. TNM stage III verses I (P = 0.01, OR=0.50), Edmondson stage II verses I (P = 0.03, OR=0.48), stage III verses stage I (P < 0.01, OR=0.30), stage IV verses I (P = 0.03, OR=0.22), and T stage T3 verses T1(P = 0.03, OR=0.22) of the CTH gene expressions were significantly lower in liver cancer. GSEA enrichment analysis result revealed that the signaling pathway most correlated with the expression of CTH and CBS genes in liver cancer cells was cytochrome P450 (CYP450) (FDR Q < 0.01, FWER P < 0.01). Western blot results showed that the expression of the CTH downstream protein CSE was reduced in HCC cell lines such as HLE and Hep3B cells compared with the human immortalized liver cell line HL-7702. Conclusion: CBS and CTH gene expressions are lower in tumor tissue than in normal tissue groups. The CBS gene is an independent risk factor for poor prognosis in stem cell carcinoma. The cytochrome P450 is the signaling pathway most closely related to the CBS and CTH genes.