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

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 ?² 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.

SUBMITTER: Zhang R

PROVIDER: S-EPMC7086244 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Zhang Rulin R Wu Junyi J Yang Yiming Y Xia Dongge D Li Jiayong J Quan Heng H Niu Ziguang Z Yang Ye Y Wu Jun J

Journal of Cancer 20200304 10

<b>Background</b>: 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. <b>Methods</b>: A total of 74 HC ...[more]

PMID: 32226523

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Project description:BackgroundLiver cancer, of which hepatocellular carcinoma (HCC) is by far the most common type, is the second most deadly cancer (746,000 deaths in 2012). Currently, the only curative treatment for HCC is surgery to remove the malignancy (resection) or to remove the entire diseased liver followed by transplantation of healthy liver tissue. Given the shortage of healthy livers, it is crucial to provide transplants to patients that have the best chance of long-term survival. Currently, transplantation is determined via the Milan criteria-patients within Milan (single tumor < 5 cm or 2-3 tumors < 3 cm with no extrahepatic spread nor intrahepatic vascular invasion) are typically eligible for transplantation. However, combining microRNA expression profiling with the Milan criteria can improve prediction of recurrence. HCC often presents with multiple distinct tumor foci arising from local spread of a primary tumor or from the oncogenic predisposition of the diseased liver. Substantial genomic heterogeneity between tumor foci within a single patient has been reported; therefore, biomarker development must account for the possibility of highly heterogeneous genomic profiles from the same individual.MethodsMicroRNA profiling was performed on 180 HCC tumor samples from 89 patients who underwent liver transplantation at the University of Rochester Medical Center. The primary outcome was recurrence-free survival time, and patients were observed for 3 years post-transplantation.ResultsMicroRNA expression profiles were used to develop a biomarker that distinguishes HCC patients at greater risk of recurrence post-transplantation. Unsupervised clustering uncovered two distinct subgroups with vast differences in standard transplantation selection criteria and recurrence-free survival times. These subgroups were subsequently used to identify microRNAs strongly associated with HCC recurrence. Our results show that reduced expression of five specific microRNAs is significantly associated with HCC recurrence post-transplantation.ConclusionsMicroRNA profiling of distinct tumor foci, coupled with methods that address within-subject tumor heterogeneity, has the potential to significantly improve prediction of HCC recurrence post-transplantation. The development of a clinically applicable HCC biomarker would inform treatment options for patients and contribute to liver transplant selection criteria for practitioners.

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

Publications

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

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