Combination of polymorphisms within the HDAC1 and HDAC3 gene predict tumor recurrence in hepatocellular carcinoma patients that have undergone transplant therapy
Combination of polymorphisms within the HDAC1 and HDAC3 gene predict tumor recurrence in hepatocellular carcinoma patients that have undergone transplant therapy
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DOI：
10.1515/cclm.2010.353
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发表时间：
2010-12-01
影响因子：
6.8
通讯作者：
Zheng, Shu-Sen
中科院分区：
文献类型：
--
作者：
Yang, Zhe;Zhou, Lin;Zheng, Shu-Sen
背景：组蛋白去乙酰化酶（HDAC）已被报道是癌症患者预后不良的指标。然而，尚无I类HDAC单核苷酸多态性（SNP）在肝细胞癌（HCC）中作用的数据。因此，我们研究了I类HDAC异构体基因多态性与肝癌和肿瘤复发的风险，肝移植（LT）后，方法：一百九十六名中国受试者组成的97例肝癌患者和99名对照组参加了这项研究。HDAC 1、HDAC 2和HDAC 3基因的9种多态性使用Applied Biosystems SNaP-Shot和TaqMan技术检测rs 2530223、rs 1741981、rs 2547547、rs 13204445、rs6568819、rs 10499080、rs 11741808、rs 2475631、rs 11391）。我们发现HCC病例组和对照组之间的基因型频率没有显著差异。在LT后肿瘤复发方面，与CC纯合子患者相比，携带HDAC 1 SNP rs 1741981 T等位基因的患者显示出良好的无复发生存结局。此外，在HDAC 3 SNP rs 2547547中观察到相同的显著趋势。Kaplan-Meier分析显示HDAC 1 SNP rs 1741981的T变异等位基因（CT+TT）和HDAC 3 SNP rs 2547547的纯合TT变异等位基因的组合是最有利的预后因素。与HDAC 1 SNP rs 1741981 CC和HDAC 3 SNP rs 2547547 CT基因型组合携带者相比，该基因型组合携带者的术后肿瘤复发风险约低2.2倍（风险比：2.235，p=0.003）。我们的数据表明，HDAC 1 SNP rs 1741981和HDAC 3 SNP rs 2547547的联合分析可能是LT患者HCC复发的潜在遗传标记。临床化学实验室医学2010; 48：1785-91。
Background: Histone deacetylases (HDACs) have been reported to be poor prognostic indicators in patients with cancer. However, no data are available for the role of single nucleotide polymorphism (SNP) of class I HDAC in hepatocellular carcinoma (HCC). Therefore, we investigated the association of class I HDAC isoforms genomic polymorphisms with risk of HCC and tumor recurrence following liver transplantation (LT).Methods: One hundred and ninety-six Chinese subjects consisting of 97 HCC patients and 99 controls were enrolled in this study. Nine polymorphisms of the HDAC1, HDAC2, and HDAC3 gene (rs2530223, rs1741981, rs2547547, rs13204445, rs6568819, rs10499080, rs11741808, rs2475631, rs11391) were examined using Applied Biosystems SNaP-Shot and TaqMan technology.Results: We found no significant difference in genotype frequencies between the HCC cases and controls. In terms of tumor recurrence following LT, patients carrying the T allele of HDAC1 SNP rs1741981 showed a favorable outcome for recurrence free survival when compared with patients homozygous for CC. In addition, the same significant trend was observed in HDAC3 SNP rs2547547. Kaplan-Meier analysis showed that the combination of the T variant allele (CT+TT) of HDAC1 SNP rs1741981 and the homozygous TT variant allele of HDAC3 SNP rs2547547 was the most favorable prognostic factor. The risk for postoperative tumor recurrence was about 2.2-fold lower for patients with this genotype combination compared with carriers of the HDAC1 SNP rs1741981 CC and HDAC3 SNP rs2547547 CT genotype combination (hazard ratio: 2.235, p=0.003).Conclusions: Our data suggest that combined analysis of HDAC1 SNP rs1741981 and HDAC3 SNP rs2547547 may be a potential genetic marker for HCC recurrence in LT patients. Clin Chem Lab Med 2010; 48:1785-91.