Genetic variations in plasma circulating DNA of HBV-related hepatocellular carcinoma patients predict recurrence after liver transplantation |
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Authors: | Hu Jie Wang Zheng Fan Jia Dai Zhi He Yi-Feng Qiu Shuang-Jian Huang Xiao-Wu Sun Jian Xiao Yong-Sheng Song Kang Shi Ying-Hong Sun Qi-Man Yang Xin-Rong Shi Guo-Ming Yu Lei Yang Guo-Huan Ding Zhen-Bin Gao Qiang Tang Zhao-You Zhou Jian |
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Institution: | Liver Cancer Institute, Zhong Shan Hospital, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, the Chinese Ministry of Education, Shanghai Key Laboratory for Organ Transplantation, Shanghai, People's Republic of China. |
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Abstract: | BackgroundRecurrence prediction of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT) present a great challenge because of a lack of biomarkers. Genetic variations play an important role in tumor development and metastasis.MethodsOligonucleotide microarrays were used to evaluate the genetic characteristics of tumor DNA in 30 HBV-related HCC patients who were underwent LT. Recurrence-related single-nucleotide polymorphism were selected, and their prognostic value was assessed and validated in two independent cohorts of HCC patients (N?=?102 and N?=?77), using pretransplant plasma circulating DNA. Prognostic significance was assessed by Kaplan-Meier survival estimates and log-rank tests. Multivariate analyses were performed to evaluate prognosis-related factors.Resultsrs894151 and rs12438080 were significantly associated with recurrence (P?=?.003 and P?=?.004, respectively). Multivariate analyses demonstrated that the co-index of the 2 SNPs was an independent prognostic factor for recurrence (P?=?.040). Similar results were obtained in the third cohort (N?=?77). Furthermore, for HCC patients (all the 3 cohorts) exceeding Milan criteria, the co-index was a prognostic factor for recurrence and survival (P<.001 and P?=?.002, respectively).ConclusionsOur study demonstrated first that genetic variations of rs894151 and rs12438080 in pretransplant plasma circulating DNA are promising prognostic markers for tumor recurrence in HCC patients undergoing LT and identify a subgroup of patients who, despite having HCC exceeding Milan criteria, have a low risk of post-transplant recurrence. |
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