结直肠癌转移相关基因 1 中的单核苷酸多态性可预测肝癌移植后的复发。
Single nucleotide polymorphisms in the metastasis-associated in colon cancer-1 gene predict the recurrence of hepatocellular carcinoma after transplantation.
机构信息
1. Key Lab of Multi-organ Transplantation, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
1. Key Lab of Multi-organ Transplantation, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, P.R. China. ; 2. Division of Hepatobiliary and Pancreatic surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
出版信息
Int J Med Sci. 2014 Jan 5;11(2):142-50. doi: 10.7150/ijms.7142. eCollection 2014.
BACKGROUND
The newly identified metastasis-associated in colon cancer-1 (MACC1) gene is involved in angiogenesis, epithelial-to-mesenchymal transition (EMT), invasiveness, and metastasis in a variety of malignancies. Overexpression of MACC1 gene is a prognostic marker for poor outcome of hepatocellular carcinoma (HCC) patients. However, the association between genetic polymorphisms of MACC1 gene and poor outcome in HCC has been not been performed. We therefore investigated the correlation of MACC1 single nucleotide polymorphisms (SNPs) with tumor recurrence and overall survival in HCC patients undergoing liver transplantation (LT).
METHODS
The study included 187 HCC patients treated with LT. Five polymorphisms in the MACC1 gene (rs1990172, rs3735615, rs4721888, rs2241056, rs975263) were genotyped in 183 cases of tumorous tissue sample and 117 cases of adjacent normal tissue sample using SNaP-Shot assays. The association of SNPs with tumor recurrence and overall survival was then analyzed by additive, dominant, recessive, and overdominant models in a cohort of 156 HCC patients.
RESULTS
In terms of tumor recurrence, heterozygous of SNP rs1990172 and SNP rs975263 showed a significant high risk of relapse using univariate and multivariate analysis (overdominant, HR(95%CI)=2.27 [1.41-3.66], P=0.001; HR(95%CI)=2.16 [1.37-3.39], P=0.001). But the difference between heterozygous of these two SNPs and overall survival did not reach a significance in all models. The other three investigated SNPs were not significantly associated with tumor recurrence and overall survival (P>0.05). In addition, we found no significant difference in genotype frequencies between HCC and controls.
CONCLUSIONS
Our data suggest that SNP rs1990172 and SNP rs975263 in the MACC1 gene may be potential genetic markers for HCC recurrence in LT patients.
背景
新鉴定的结肠癌转移相关基因 1（MACC1）参与多种恶性肿瘤的血管生成、上皮间质转化（EMT）、侵袭和转移。MACC1 基因的过表达是肝细胞癌（HCC）患者预后不良的标志物。然而，MACC1 基因的遗传多态性与 HCC 不良预后之间的关系尚未得到研究。因此，我们研究了 MACC1 单核苷酸多态性（SNP）与接受肝移植（LT）的 HCC 患者肿瘤复发和总生存的相关性。
方法
本研究纳入了 187 例接受 LT 治疗的 HCC 患者。采用 SNaP-Shot 法对 183 例肿瘤组织样本和 117 例相邻正常组织样本中的 MACC1 基因（rs1990172、rs3735615、rs4721888、rs2241056、rs975263）的 5 个 SNP 进行基因分型。然后，在 156 例 HCC 患者的队列中，采用加性、显性、隐性和超显性模型分析 SNP 与肿瘤复发和总生存的关系。
结果
在肿瘤复发方面，SNP rs1990172 和 SNP rs975263 的杂合子在单因素和多因素分析中显示出显著的高复发风险（超显性，HR（95%CI）=2.27[1.41-3.66]，P=0.001；HR（95%CI）=2.16[1.37-3.39]，P=0.001）。但在所有模型中，这两个 SNP 的杂合子与总生存之间的差异没有达到显著性。另外三个研究的 SNP 与肿瘤复发和总生存均无显著相关性（P>0.05）。此外，我们没有发现 HCC 患者和对照组之间基因型频率有显著差异。
结论
我们的数据表明，MACC1 基因中的 SNP rs1990172 和 SNP rs975263 可能是 LT 患者 HCC 复发的潜在遗传标志物。
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