PLoS ONE (Jan 2011)

Genetic variations in plasma circulating DNA of HBV-related hepatocellular carcinoma patients predict recurrence after liver transplantation.

  • Jie Hu,
  • Zheng Wang,
  • Jia Fan,
  • Zhi Dai,
  • Yi-Feng He,
  • Shuang-Jian Qiu,
  • Xiao-Wu Huang,
  • Jian Sun,
  • Yong-Sheng Xiao,
  • Kang Song,
  • Ying-Hong Shi,
  • Qi-Man Sun,
  • Xin-Rong Yang,
  • Guo-Ming Shi,
  • Lei Yu,
  • Guo-Huan Yang,
  • Zhen-Bin Ding,
  • Qiang Gao,
  • Zhao-You Tang,
  • Jian Zhou

DOI
https://doi.org/10.1371/journal.pone.0026003
Journal volume & issue
Vol. 6, no. 10
p. e26003

Abstract

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BACKGROUND:Recurrence 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. METHODS:Oligonucleotide 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. RESULTS:rs894151 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). CONCLUSIONS:Our 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.