title: A functional copy-number variation in MAPKAPK2 predicts risk and prognosis of lung cancer.
abstract: Mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2) may promote cancer development and progression by inducing tumorigenesis and drug resistance. To assess whether the copy-number variation g.CNV-30450 located in the MAPKAPK2 promoter has any effect on lung cancer risk or prognosis, we investigated the association between g.CNV-30450 and cancer risk in three independent case-control studies of 2,332 individuals with lung cancer and 2,457 controls and the effects of g.CNV-30450 on cancer prognosis in 1,137 individuals with lung cancer with survival data in southern and eastern Chinese populations. We found that those subjects who had four copies of g.CNV-30450 had an increased cancer risk (odds ratio = 1.94, 95% confidence interval [CI] = 1.61-2.35) and a worse prognosis for individuals with lung cancer (with a median survival time of only 9 months) (hazard ratio = 1.47, 95% CI = 1.22-1.78) compared with those with two or three copies (with a median survival time of 14 months). Meanwhile, four copies of g.CNV-30450 significantly increased MAPKAPK2 expression, both in vitro and in vivo, compared with two or three copies. Our study establishes a robust association between the functional g.CNV-30450 in MAPKAPK2 and risk as well as prognosis of lung cancer, and it presents this functional copy-number variation as a potential biomarker for susceptibility to and prognosis for lung cancer.
authors.affiliation: Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Binfang
authors.initials: B
authors.lastname: Huang
authors.forename: Mei
authors.initials: M
authors.lastname: Cheng
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Yinyan
authors.initials: Y
authors.lastname: Li
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Huang
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.forename: Qingchu
authors.initials: Q
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Weidong
authors.initials: W
authors.lastname: Ji
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jiachun
authors.initials: J
authors.lastname: Lu
mesh_terms: D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D056915:DNA Copy Number Variations / Q000235:genetics*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D016017:Odds Ratio; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D005819:Genetic Markers; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D000099190:MAP-Kinase-Activated Kinase 2