Caspase polymorphisms and prognosis of hepatocellular carcinoma

<div><p>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 <i>CASP3</i>, <i>CASP7</i>, <i>CASP8</i>, <i>CASP9</i>, <i>CASP10</i> 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 <i>CASP9</i> rs4645981 C allele was significantly associated with positive effect on DFS (<i>P</i> = 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 (<i>P</i> = 0.048 and 0.041, respectively). Moreover, the <i>CASP3</i> rs2705897 GT genotype showed marginally significant association with decreased OS and DFS, compared with the GG genotype. One haplotype TT/TG in <i>CASP3</i> (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 (<i>P</i> = 0.021 and 0.026, respectively) and multivariate analysis (<i>P</i> = 0.025 and 0.030, respectively). The haplotype GT/GT in <i>CASP9</i> (constructed by rs4645978 A>G and rs4645981 C>T) was significantly associated with decreased DFS both in univariate and multivariate analysis (<i>P</i> = 0.012 and 0.010, respectively). In conclusion, the <i>CASP9</i> rs4645981 polymorphism, <i>CASP3</i> and <i>CASP9</i> haplotypes may be useful prognosis markers for HCC patients with surgical resection of tumor.</p></div

Kaplan-Meier survival curves of <i>CASP9</i>_haplotype with disease free survival of HCC patients.

<p>Kaplan-Meier survival curves of <i>CASP9</i>_haplotype with disease free survival of HCC patients.</p

Kaplan-Meier survival curves of <i>CASP9</i> rs4645981 with clinical outcomes of 362 HCC patients.

<p>(A) disease free survival (DFS) (B) overall survival (OS).</p

Univariate and multivariate Cox regression analysis of genotypes in HCC patients.

<p>Univariate and multivariate Cox regression analysis of genotypes in HCC patients.</p

Kaplan-Meier survival curves of <i>CASP3</i>_haplotype with clinical outcomes of HCC patients.

<p>(A) overall surviva<i>l</i> (OS), and (B) disease free survival (DFS).</p

SNPs selected in CASP genes and their allele frequencies.

<p>SNPs selected in CASP genes and their allele frequencies.</p

Clinical characteristics and their prediction of overall survival and disease free survival in HCC patients.

<p>Clinical characteristics and their prediction of overall survival and disease free survival in HCC patients.</p