Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
Gene. 2019 Mar 20;689:97-101. doi: 10.1016/j.gene.2018.11.035. Epub 2018 Dec 7.
Many enzymes involved in one‑carbon metabolism (OCM) are considered to have important roles in carcinogenesis, especially in hepatocellular carcinoma (HCC). However, the influence of polymorphisms in OCM genes on recurrence in HCC patients with liver transplantation has yet not been reported. The aim of this study was to explore the impact of donor liver graft OCM gene polymorphism on the prognosis of liver transplant recipients with HCC.
This study enrolled 100 liver transplantation patients from a Chinese Han population to detect the association between donor OCM genes polymorphisms and post-transplant HCC recurrence. Nine SNPs from seven OCM genes (MTHFD1, MTR, MTRR, DHFR, ALDH1L1, SHMT1, and CBS) were evaluated by Chi-square test and Kaplan-Meier survival analysis.
None of the nine SNPs were significantly associated with cancer recurrence after liver transplantation. However, tumor-free survival for recipients with the AA genotype of rs1801394 polymorphism was significantly shorter than patients with AG/GG genotype (1097 ± 155 vs. 1657 ± 173 days, P < 0.05) among patients with alpha-fetoprotein < 400 ng/ml. Kaplan-Meier survival curves showed that recipients with donor rs1127717 homozygous TT had a significantly longer tumor-free survival and overall survival than heterozygous CT/CC recipients (tumor-free survival 1395 ± 128 vs. 671 ± 233 days, P < 0.05; overall survival 1540 ± 114 vs. 925 ± 242 days, P < 0.05) in the patient subgroup with well or moderately differentiated HCC.
This is the first genetic study to examine the relation between donor liver graft OCM gene polymorphisms and the risk of HCC recurrence after liver transplantation. Our findings support the hypothesis that polymorphisms of donor genes related to OCM play important roles in post-transplant HCC recurrence. Furthermore, donor rs1801394 and rs1127717 polymorphism may serve as promising prognostic biomarkers for HCC recurrence in liver transplant recipients.
许多参与一碳代谢（OCM）的酶被认为在癌症发生中具有重要作用，尤其是在肝细胞癌（HCC）中。然而，OCM 基因多态性对肝移植 HCC 患者复发的影响尚未报道。本研究旨在探讨供肝 OCM 基因多态性对 HCC 肝移植受者预后的影响。
本研究纳入了 100 例来自汉族人群的肝移植患者，以检测供体 OCM 基因多态性与移植后 HCC 复发之间的关系。通过卡方检验和 Kaplan-Meier 生存分析评估了来自七个 OCM 基因（MTHFD1、MTR、MTRR、DHFR、ALDH1L1、SHMT1 和 CBS）的 9 个 SNP。
九个 SNP 均与肝移植后癌症复发无显著相关性。然而，在 AFP<400ng/ml 的患者中，rs1801394 多态性 AA 基因型的受者无肿瘤存活期明显短于 AG/GG 基因型（1097±155 vs. 1657±173 天，P<0.05）。Kaplan-Meier 生存曲线显示，供体 rs1127717 纯合 TT 的受者无肿瘤存活期和总存活期明显长于杂合 CT/CC 受者（无肿瘤存活期 1395±128 vs. 671±233 天，P<0.05；总存活期 1540±114 vs. 925±242 天，P<0.05）在 HCC 分化良好或中等的患者亚组中。
这是首次研究供体肝移植 OCM 基因多态性与肝移植后 HCC 复发风险之间关系的遗传研究。我们的研究结果支持这样的假设，即与 OCM 相关的供体基因多态性在移植后 HCC 复发中起着重要作用。此外，供体 rs1801394 和 rs1127717 多态性可能成为预测 HCC 肝移植受者复发的有前途的预后生物标志物。
