Caspase polymorphisms and prognosis of hepatocellular carcinoma.
Caspase polymorphisms and prognosis of hepatocellular carcinoma.
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Caspase多态性与肝细胞癌的预后
DOI：
10.1371/journal.pone.0176802
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Jiang DK
中科院分区：
文献类型：
--
作者：
Zhang S;Xiao Q;Shi Z;Yu G;Ma XP;Chen H;Zhang P;Shen S;Sai-Yin HG;Chen TY;Lu PX;Wang NJ;Ren W;Huang P;Xie J;Conran C;Zheng SL;Yu L;Xu J;Jiang DK
本研究的目的是探讨半胱天冬酶（CASP）基因多态性对肝细胞癌（HCC）预后的影响。我们对362例接受手术切除的肝癌患者的CASP 3、CASP 7、CASP 8、CASP 9、CASP 10基因的7个潜在功能多态性进行了基因分型。采用考克斯比例风险模型分析基因型和单倍型与总生存期（OS）和无病生存期（DFS）的关系。我们发现CASP 9 rs 4645981 C等位基因与DFS的正效应显著相关（单因素和多因素分析中CT+CC vs. TT的P值分别为0.011和0.016），单因素和多因素分析中CT基因型与HCC的OS均优于TT基因型（P值分别为0.048和0.041）。此外，与GG基因型相比，CASP 3 rs 2705897 GT基因型显示出与OS和DFS降低的轻微显著相关性。在单因素分析（P = 0.021和0.026）和多因素分析（P = 0.025和0.030）中，与常见单倍型TT/TT相比，CASP 3中的一种单倍型TT/TG（由rs 12108497 T>C和rs 2705897 T>G构建）与OS和DFS降低显著相关。在单因素和多因素分析中，CASP 9单倍型GT/GT（由rs 4645978 A>G和rs 4645981 C>T构建）与DFS降低显著相关（分别为P = 0.012和0.010）。结论：CASP 9基因rs 4645981多态性、CASP 3和CASP 9单倍型可能是HCC患者手术切除的预后指标。
The aim of our study was to determine the impact of genetic polymorphisms in the caspase (CASP) genes on prognosis of hepatocellular carcinoma (HCC). We genotyped 7 potentially functional polymorphisms in CASP3, CASP7, CASP8, CASP9, CASP10 genes in 362 HCC patients of receiving surgical resection of HCC tumor. The associations of genotype and haplotype with overall survival (OS) and disease free survival (DFS) were analyzed by using the Cox proportional hazards model. We found that the CASP9 rs4645981 C allele was significantly associated with positive effect on DFS (P = 0.011 and 0.016 for CT+CC vs. TT in univariate and multivariate analysis, respectively), CT genotype was associated with a better OS of HCC than the TT genotype both in univariate and multivariate analysis (P = 0.048 and 0.041, respectively). Moreover, the CASP3 rs2705897 GT genotype showed marginally significant association with decreased OS and DFS, compared with the GG genotype. One haplotype TT/TG in CASP3 (constructed by rs12108497 T>C and rs2705897 T>G) was significantly associated with decreased OS and DFS, compared to the common haplotype TT/TT both in univariate analysis (P = 0.021 and 0.026, respectively) and multivariate analysis (P = 0.025 and 0.030, respectively). The haplotype GT/GT in CASP9 (constructed by rs4645978 A>G and rs4645981 C>T) was significantly associated with decreased DFS both in univariate and multivariate analysis (P = 0.012 and 0.010, respectively). In conclusion, the CASP9 rs4645981 polymorphism, CASP3 and CASP9 haplotypes may be useful prognosis markers for HCC patients with surgical resection of tumor.