Abstract
Background: Our previous studies have reported that polycomb chromobox 4 (CBX4) has a potential promoting hepatocellular carcinoma (HCC) angiogenesis and tumor progression. However, it is unclear whether genetic single-nucleotide polymorphisms (SNPs) in this gene are associated with HCC prognosis. Methods: We conducted a hospital-based two-phase study, including 598 patients with pathologically diagnosed HCC for the SNPs screening phase and 328 HCC patients for clinic significance validating phase, to elucidate the association between SNPs of CBX4 and the survival of HCC. The genotypes of CBX4 were tested using the SNaPshot method and the effects of CBX4 SNPs on HCC prognosis were analyzed using Kaplan-Meier survival model and Cox regression model. Results: A total of 33 SNPs were selected and genotyped in this study. We found the rs77447679 SNP was significantly related to survival in individuals with HCC. Specifically, survival was noticeably decreased in HCC patients who have mutant homozygote AA of this SNP (rs77447679-AA) compared with these with wild type (rs77447679-CC). An additive effect of rs77447679 polymorphism and aflatoxin B1 exposure level was also observed in the survival analyses of HCC cases. Furthermore, this SNP was positively correlated not only with tumor size, grade, stage, and microvessel density (correlation coefficient r = 0.17, 0.23, 0.23, and 0.42, respectively), but also with increasing CBX4 expression (r = 0.57). Interestingly, the mutant genotypes of rs77447679 can significantly improve the therapeutic response of HCC cases on post-operative adjuvant transarterial chemoembolization (pa-TACE), but wild type not. Conclusions: These data suggest that genetic polymorphisms in the CBX4 may be a prognostic biomarker for HCC, and the rs77447679 SNP is such a potential candidate.
Highlights
Liver cancer is the second-leading cause of malignancy-associated deaths worldwide, and more than 85% of patients have hepatocellular carcinoma (HCC) [1]
Results from Cox regression analyses displayed that the patients having high aflatoxin B1 (AFB1) exposure featured a higher death risk (HR = 2.46, 95% confidence interval (CI) = 1.99–3.04) and tumor recurrence risk (HR = 5.15, 95% confidence interval (95% CI) = 3.56–7.45)
4.4 Multivariable analyses indicating chromobox 4 (CBX4) rs77447679 single nucleotide polymorphism (SNP) as an independent prognostic factor for patients with HCC. Because clinicopathological features such as bigger tumor size, higher microvessel density (MVD), and lower tumor grade are correlated with poor HCC survival, we aimed to pinpoint whether reduced survival among patients with risk genotypes of rs77447679 was an indirect reflection of relationship between the CBX4 rs77447679 SNP and these clinicopathological features or, alternately, whether CBX4 rs77447679 SNP could act as an independent biomarker for HCC survival
Summary
Liver cancer is the second-leading cause of malignancy-associated deaths worldwide, and more than 85% of patients have hepatocellular carcinoma (HCC) [1]. Discovery of biomarkers for the early-stage diagnosis and prognostic prediction of this cancer may improve the outcome of patients with HCC. Our previous studies have displayed that the dysregulation of CBX4 progress hepatocarcinoma angiogenesis and affects the prognosis of patients with HCC [8,9,10]. Several reports have been indicative of genetic variants in this gene [11, 12]. It is not clear whether genetic single nucleotide polymorphisms (SNPs) in CBX4 modify HCC prognosis. We conducted a hospital-based retrospective study to explore the association between CBX4 SNPs and the outcome of HCC in the Guangxi Region, a high incidence area of this malignancy
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