A genetic variant in large tumor suppressor kinase 2 of Hippo signaling pathway contributes to prognosis of hepatocellular carcinoma.
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.
Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People's Republic of China; Department of Oncology, Haimen People's Hospital, Haimen, People's Republic of China.
Lili
L
Shen
Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital Affiliated with Nanjing Medical University, Nanjing, People's Republic of China; Department of Epidemiology and Biostatistics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
Juan
J
Wen
Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
Tingting
T
Zhao
Department of Epidemiology and Biostatistics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, People's Republic of China.
Zhibin
Z
Hu
Department of Epidemiology and Biostatistics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
Ci
C
Song
Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
Dongying
D
Gu
Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, People's Republic of China.
Mingliang
M
He
Department of Surgery, The University of Hong Kong, Hong Kong, People's Republic of China.
Nikki P
NP
Lee
Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
Zhi
Z
Xu
Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
Jinfei
J
Chen
LATS2; hepatocellular carcinoma; prognosis; retrospective study; single-nucleotide polymorphism