A genetic variant in large tumor suppressor kinase 2 of Hippo signaling pathway contributes to prognosis of hepatocellular carcinoma.
A genetic variant in large tumor suppressor kinase 2 of Hippo signaling pathway contributes to prognosis of hepatocellular carcinoma.
复制标题
Hippo信号通路大肿瘤抑制激酶2的遗传变异有助于肝细胞癌的预后
DOI：
10.2147/ott.s100699
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发表时间：
2016
影响因子：
4
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Shen L;Wen J;Zhao T;Hu Z;Song C;Gu D;He M;Lee NP;Xu Z;Chen J
Hippo通路在肝细胞癌（HCC）的发生发展中起着重要作用。本研究旨在探讨Hippo通路相关基因的遗传变异及其与肝癌预后的关系。本研究共招募了331例B型肝炎表面抗原检测阳性的HCC患者。所有患者均未接受过手术治疗。12个潜在功能性单核苷酸多态性（LATS 2中的rs7317471和rs9509492; MST 1中的rs4810446、rs2267853、rs8000和rs6073627; MST 2中的rs10955176;以及TAZ中的rs16861979、rs2043550、rs16861985、rs1055153和rs7630434）使用Sequenom MassARRAY iPLEX平台从患者的外周血白细胞进行基因分型。生存分析采用考克斯比例风险模型和对数秩检验。LATS 2 rs7317471 C> T多态性与使用显性模型的HCC死亡风险降低显著相关（校正的风险比[HR]= 0.63，95%置信区间[CI]= 0.46 - 0.87，P = 0.004）。此外，使用分层分析，发现LATS 2 rs7317471 CT/TT基因型与53岁以下患者的死亡风险降低显著相关（校正HR = 0.50），女性（校正HR = 0.60），吸烟者（校正HR = 0.56），饮酒者（校正HR = 0.58），患有巴塞罗那诊所肝癌B期（校正HR = 0.62），既往未接受化疗或经导管肝动脉化疗栓塞（校正HR = 0.48）。我们的研究结果表明LATS 2 rs7317471可作为预测HCC预后的潜在生物标志物。
The Hippo pathway plays an important role in the development of hepatocellular carcinoma (HCC). The present study aimed at exploring the genetic variants of Hippo pathway-related genes and their association with HCC prognosis. A total of 331 HCC patients who tested positive for hepatitis B surface antigen were recruited in this study. None of the patients had prior surgical treatment. Twelve potentially functional single-nucleotide polymorphisms (rs7317471 and rs9509492 in LATS2; rs4810446, rs2267853, rs8000, and rs6073627 in MST1; rs10955176 in MST2; and rs16861979, rs2043550, rs16861985, rs1055153, and rs7630434 in TAZ) in the Hippo pathway were genotyped from patients’ peripheral leukocytes using the Sequenom MassARRAY iPLEX platform. Cox proportional hazard models and log-rank test were used for the survival analyses. LATS2 rs7317471 C>T polymorphism was significantly associated with decreased risk of death in HCC using the dominant model (adjusted hazard ratio [HR] =0.63, 95% confidence interval [CI] =0.46–0.87, P=0.004). Furthermore, using stratified analysis, LATS2 rs7317471 CT/TT genotypes were found to be significantly associated with decreased risk of death in patients who were below 53 years of age (adjusted HR =0.50), females (adjusted HR =0.60), smokers (adjusted HR =0.56), drinkers (adjusted HR =0.58), have Barcelona clinic liver cancer stage B (adjusted HR =0.62), and received no prior chemotherapy or transcatheter hepatic arterial chemoembolization (adjusted HR =0.48). Our results suggested that LATS2 rs7317471 could be used as a potential biomarker for the prediction of HCC prognosis.