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A genetic variant in large tumor suppressor kinase 2 of Hippo signaling pathway contributes to prognosis of hepatocellular carcinoma

Authors Shen L, Wen J, Zhao T, Hu Z, Song C, Gu D, He M, Lee N, Xu Z, Chen J

Received 17 November 2015

Accepted for publication 10 January 2016

Published 4 April 2016 Volume 2016:9 Pages 1945—1951

DOI https://doi.org/10.2147/OTT.S100699

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr William Cho


Lili Shen,1,2,* Juan Wen,3,4,* Tingting Zhao,1 Zhibin Hu,4,5 Ci Song,4 Dongying Gu,1 Mingliang He,6 Nikki P Lee,7 Zhi Xu,1 Jinfei Chen1

1Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 2Department of Oncology, Haimen People’s Hospital, Haimen, 3Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital Affiliated with Nanjing Medical University, Nanjing, 4Department of Epidemiology and Biostatistics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, 5State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, 6Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, 7Department of Surgery, The University of Hong Kong, Hong Kong, People’s Republic of China

*These authors contributed equally to this work

Abstract: 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.

Keywords: hepatocellular carcinoma, LATS2, prognosis, retrospective study, single-nucleotide polymorphism

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