J Cancer 2020; 11(10):3082-3088. doi:10.7150/jca.39712

Research Paper

Donor polymorphisms of Rap1A rs494453 contribute to a higher risk of hepatocellular carcinoma recurrence following liver transplantation

Rulin Zhang1*, Junyi Wu2*, Yiming Yang3*, Dongge Xia1, Jiayong Li1, Heng Quan1, Ziguang Niu1, Ye Yang4✉, Jun Wu1,5✉

1. Department of Laboratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China
2. Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China
3. School of Life Science, Shanghai University, Shanghai, People's Republic of China
4. Department of Gastroenterology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, People's Republic of China
5. Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
*Rulin Zhang, Junyi Wu and Yiming Yang contributed equally to this work

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Citation:
Zhang R, Wu J, Yang Y, Xia D, Li J, Quan H, Niu Z, Yang Y, Wu J. Donor polymorphisms of Rap1A rs494453 contribute to a higher risk of hepatocellular carcinoma recurrence following liver transplantation. J Cancer 2020; 11(10):3082-3088. doi:10.7150/jca.39712. Available from http://www.jcancer.org/v11p3082.htm

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Abstract

Background: Hepatocellular carcinoma (HCC) recurrence appears commonly after liver transplantation (LT), and it severely affected the long-term survival of patients. Previous studies have proved that Rap1A is involved in hepatocarcinogenesis and metastasis, and demonstrated the significant association between Rap1A gene rs494453 polymorphism and HCC. However, the relationship between Rap1A rs494453 polymorphism and HCC recurrence after LT remained unclear.

Methods: A total of 74 HCC patients who underwent LT from July 2005 to June 2015 was analyzed. The genotypes of both donors and recipients had been confirmed as Rap1A rs494453. The independent risk factors that associated with HCC recurrence were investigated with univariate and multivariate logistic regression analysis. The recurrence-free (RFS) and overall survival (OS) were calculated with Cox regression analysis. The Rap1A rs494453 genotype frequencies were determined using the Χ² test and the minor allele frequencies (MAFs) of Rap1A rs494453 genotypes were calculated by Hardy-Weinberg equilibrium.

Results: We found that the donor Rap1A rs494453 polymorphism was profoundly associated with HCC recurrence after LT. Moreover, the Milan criteria, microvascular invasion and donor Rap1A rs494453 genotype were proved to be independent risk factors for HCC recurrence. Patients with donor AG/GG genotypes had a distinct lower RFS and OS than AA genotype. The TNM stage, Milan criteria, microvascular invasion, and donor Rap1A rs494453 genotype were independent factors for the RFS of LT patients.

Conclusions: Donor Rap1A rs494453 is a potential predictive marker for HCC recurrence risk after LT.

Keywords: Rap1A polymorphism, hepatocellular carcinoma, recurrence, liver transplantation