摘要
目的探究肝癌和胱硫醚β-合成酶(cystathionineβ-synthase,CBS)基因及胱硫醚γ-裂解酶(cystathionine-γ-lyase,CTH)基因的关系。方法通过挖掘GEO(gene expression omnibus)与TCGA(the cancer genome atlas)数据库,对肝癌的临床特征与CBS及CTH基因表达进行了相关性分析。并通过对肝癌细胞系进行免疫印迹验证。结果CBS及CTH在肿瘤中的表达较非肿瘤明显降低(P<0.05)。Cox回归结果显示CBS是肝细胞癌不良预后的独立危险因素(HR=0.65,P=0.02)。针对CBS基因对不同肿瘤分期进行单因素logistics回归分析,发现肝癌TNM分期II期比I期(P=0.01,OR=0.50)、III期比I期(P=0.03,OR=0.56)、T分期T2期比T1期(P<0.01,OR=0.43)、T3期比T1期(P=0.02,OR=0.54)CBS基因显著降低。肝癌TNM分期III期比I期(P=0.01,OR=0.50),Edmondson分期II期比I期(P=0.03,OR=0.48),III期比I期(P<0.01,OR=0.30),IV期比I期(P=0.03,OR=0.22)CTH基因表达显著降低。GSEA富集分析结果显示,与肝癌细胞CTH与CBS基因表达相关性最高的信号通路为细胞色素P450(FDR Q<0.01,FWER P<0.01)。免疫印迹结果显示,与人肝永生化细胞系HL-7702相比,HLE和Hep3B细胞等肝细胞癌细胞系中CTH下游蛋白CSE表达降低。结论肿瘤组织中的CBS及CTH基因表达低于正常组织。CBS基因是肝细胞癌不良预后的独立危险因素。与CBS及CTH基因关系最为密切的是信号通路为细胞色素P450通路。
Objective To study the relationship between cystathionineβ-synthase(CBS)and cystathionineγ-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.
出处
《中华肝脏病杂志》
CAS
CSCD
北大核心
2023年第11期1169-1175,共7页
Chinese Journal of Hepatology
