IMR Press / FBL / Volume 26 / Issue 11 / DOI: 10.52586/5019
Open Access Original Research
The predictive potential of genetic single nucleotide polymorphisms in CBX4 for hepatocellular carcinoma survival
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1 Medical College, Guangxi University, 530004 Nanning, Guangxi, China
2 Clinical Pathological Diagnosis & Research Centra, the Affiliated Hospital of Youjiang Medical University for Nationalities, 533000 Baise, Guangxi, China
3 Department of Tumor Pathology, the Key Laboratory of Molecular Pathology (Hepatobiliary Diseases) of Guangxi, 533000 Baise, Guangxi, China
4 Department of Infective Diseases, the Affiliated Hospital of Youjiang Medical University for Nationalities, 533000 Baise, Guangxi, China
*Correspondence:; (Xi-Dai Long)
These authors contributed equally.
Front. Biosci. (Landmark Ed) 2021, 26(11), 1191–1203;
Submitted: 23 July 2021 | Revised: 20 October 2021 | Accepted: 2 November 2021 | Published: 30 November 2021
(This article belongs to the Special Issue Utilizationof liver cancer biomarkers)
Copyright: © 2021 The Author(s). Published by BRI.
This is an open access article under the CC BY 4.0 license (

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.

Fig. 1.
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