The prognostic impacts of TEA domain (TEAD) transcription factor polymorphisms in Chinese hepatocellular carcinoma patients
The prognostic impacts of TEA domain (TEAD) transcription factor polymorphisms in Chinese hepatocellular carcinoma patients
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TEA结构域（TEAD）转录因子多态性对中国肝癌患者预后的影响
DOI：
10.18632/oncotarget.19310
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发表时间：
2017-07
期刊：
影响因子：
--
通讯作者：
Zhi Xu
中科院分区：
文献类型：
--
作者：
Haiyan Xia;Juan Wen;Weiyong Zhao;Dongying Gu;Zhibin Hu;Jinfei Chen;Zhi Xu
TEA结构域（TEAD）转录因子通过调控多个基因的表达，在肝细胞癌（HCC）的发生发展中发挥重要作用。然而，它们的遗传变异与HCC预后的关联仍然是难以捉摸的。使用Sequenom MassARRAY iPLEX平台对331例B型肝炎病毒阳性HCC患者的TEAD 1 -4中的7个潜在功能性单核苷酸多态性（rs 2304733、rs 10831923、rs 12104362、rs3745305、rs 11756089、rs 2076173、rs7135838）进行基因分型。TEAD 3 rs 2076173 C等位基因和rs 11756089 T等位基因被确定为保护性等位基因，因为它们与较长的中位总生存时间（MST）显著相关。rs 2076173的T等位基因与HCC生存率显著相关，与年龄、性别、吸烟和饮酒状况、BCLC分期、化疗或TACE状态无关（HR = 0.73，95%CI = 0.56-0.93，P = 0.012）。这种保护作用在不饮酒的患者中更为突出（乘法交互作用P = 0.002）。携带1个以上保护性等位基因的患者MST为19.25个月，显著长于不携带者（MST=12.85个月，校正HR = 0.56，95%CI = 0.33-0.95，P=0.030），尤其是不饮酒者（校正HR = 0.48，95%CI = 0.32-0.74，P = 0.001）。提示TEAD 3基因rs 2076173和rs 11756089可作为中国人肝癌患者生存率的遗传标记。
TEA domain (TEAD) transcription factors play an important role in hepatocellular carcinoma (HCC) development and progression by regulating the expression of a number of genes. However, the association of their genetic variations with HCC prognosis remains elusive. Seven potentially functional single nucleotide polymorphisms in TEAD1-4 (rs2304733, rs10831923, rs12104362, rs3745305, rs11756089, rs2076173, rs7135838) were genotyped from 331 hepatitis B virus positive HCC patients using the Sequenom MassARRAY iPLEX platform. The TEAD3 rs2076173 C allele and rs11756089 T allele were identified as protective alleles as they were significantly associated with longer median overall survival time (MST). The T allele of rs2076173 was significantly associated with HCC survival independent of age, gender, smoking and drinking status, BCLC stage, and chemotherapy or TACE status (HR = 0.73, 95% CI = 0.56-0.93, P = 0.012). This protective effect was more prominent for patients who were non-drinkers (P for multiplicative interaction = 0.002). Patients had more than one of these protective alleles had significant longer MST of 19.25 months than those had none (MST=12.85 months, adjusted HR = 0.56, 95% CI = 0.33-0.95, P=0.030), especially for those non-drinkers (adjusted HR = 0.48, 95% CI = 0.32-0.74, P = 0.001). These findings suggested that rs2076173 and rs11756089 in TEAD3 gene could serve as genetic markers for favorable survival in the Chinese HCC patients.