Association of WWOX rs9926344 polymorphism with poor prognosis of hepatocellular carcinoma.
Association of WWOX rs9926344 polymorphism with poor prognosis of hepatocellular carcinoma.
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WWOX rs9926344多态性与肝细胞癌不良预后的关系
DOI：
10.7150/jca.23808
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发表时间：
2018
影响因子：
3.9
通讯作者：
Ren N
中科院分区：
文献类型：
--
作者：
Chen W;Zhou C;Zhang W;Atyah M;Yin Y;Guo L;Tang W;Dong Q;Ye Q;Ren N
简介：含有WW结构域的氧化还原酶（WWOX）基因在人体组织中广泛表达，被认为是一种抑癌基因，在包括肝癌在内的人类肿瘤的发生和发展中起重要作用。本研究旨在探讨WWOX基因单核苷酸多态性（SNPs）与肝细胞癌（HCC）患者预后的关系。材料与方法：共招募152例HCC患者，随机选择8例术后2年内肿瘤复发和8例未复发的患者，使用AffysseArray 6.0进行SNP基因分型和筛查。然后，我们通过飞行时间质谱法（TOF-MS）确认了其余136例患者中的候选SNP。结果如下：总共筛选并鉴定了32个SNP作为候选SNP，特别是一个SNP（rs 9926344），其被进一步证实是有价值的。我们发现WWOX rs 9926344的AA+AG基因型和A等位基因与HCC复发风险显著相关（分别为p=0.002和p=0.001）。Kaplan-Meier曲线显示rs 9926344 AA +AG基因型患者的RFS（P=0.004）和OS（P=0.005）均低于GG基因型患者。多因素考克斯回归分析显示AA+AG基因型是影响肿瘤复发的独立预后因素（HR 1.787，95%CI 1.042-3.064，P=0.035）。免疫组化结果显示，AG基因型患者的WWOX蛋白表达下调频率高于GG基因型患者（P=0.023）。结论：我们的研究结果表明，WWOX rs 9926344多态性与肿瘤复发呈正相关，可作为HCC患者术后独立的预后指标。
Introduction: The WW domain-containing oxidoreductase (WWOX), widely expressed in human tissues, is considered as a tumor suppressor gene and plays an important role in the incidence and progression of human cancer, HCC included. This study was to investigate the correlation between single nucleotide polymorphisms (SNPs) of the WWOX gene and the prognosis of hepatocellular carcinoma (HCC) patients. Materials and Methods: After a total of 152 HCC patients were recruited, 8 cases with tumor recurrence within 2-years after operation and 8 cases without recurrence were selected randomly for SNP genotyping and screening using Affymetrix Array 6.0. And then we confirmed candidate SNPs in the remaining 136 patients by time-of-flight mass spectrometry (TOF-MS). Results: In total, 32 SNPs were screened and identified as candidate SNPs with one SNP in particular, (rs9926344), being further verified to be valuable. We found that AA+AG genotype and A allele of WWOX rs9926344 were significantly associated with recurrent risk of HCC (p=0.002 and p=0.001, respectively). The Kaplan-Meier curve showed that patients carrying rs9926344 AA +AG genotype had poor RFS (P=0.004) and OS (P=0.005) compared to those carrying GG genotypes. The multivariate COX regression analysis showed that the AA+AG genotype were an independent prognostic factor for tumor recurrence (HR 1.787, 95% CI 1.042-3.064, P=0.035). Furthermore, IHC analysis showed that the WWOX protein down-regulation is more frequent in patients with AG genotype compared to those with GG genotype (P=0.023). Conclusion: Our findings indicate that WWOX rs9926344 polymorphism is positively correlated with tumor recurrence and can be used as an independent prognostic marker for HCC patients after operation.
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影响因子：
29.4
作者：
El-Serag HB
通讯作者：
El-Serag HB
影响因子：
3.7
作者：
Lee HL;Cheng HL;Liu YF;Chou MC;Yang SF;Chou YE
通讯作者：
Chou YE
影响因子：
1.3
作者：
Liu W;Golovatch S;Tian M
通讯作者：
Tian M
影响因子：
2.8
作者：
Guo, Wei;Dong, Zhiming;Yang, Zhibin
通讯作者：
Yang, Zhibin
DOI：
10.1073/pnas.1315934110
发表时间：
2013-10-15
影响因子：
11.1
作者：
Gonzalez-Garay, Manuel L.;McGuire, Amy L.;Caskey, C. Thomas
通讯作者：
Caskey, C. Thomas