Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, China.
Am J Hum Genet. 2012 Aug 10;91(2):384-90. doi: 10.1016/j.ajhg.2012.07.003.
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.
丝裂原活化蛋白激酶激活的蛋白激酶 2（MAPKAPK2）可通过诱导肿瘤发生和耐药来促进癌症的发展和进展。为了评估位于 MAPKAPK2 启动子中的 g.CNV-30450 拷贝数变异是否对肺癌风险或预后有任何影响，我们在三个独立的病例对照研究中研究了 g.CNV-30450 与 2332 名肺癌患者和 2457 名对照者的癌症风险之间的关联，以及 g.CNV-30450 对来自中国南方和东部人群的 1137 名具有生存数据的肺癌患者的癌症预后的影响。我们发现，那些具有四个 g.CNV-30450 拷贝的受试者具有更高的癌症风险（比值比=1.94，95%置信区间[CI] = 1.61-2.35）和更差的肺癌预后（中位生存时间仅为 9 个月）（风险比=1.47，95%CI = 1.22-1.78）与具有两个或三个拷贝的患者（中位生存时间为 14 个月）相比。同时，与两个或三个拷贝相比，g.CNV-30450 的四个拷贝在体外和体内均显著增加了 MAPKAPK2 的表达。我们的研究确立了 MAPKAPK2 中功能性 g.CNV-30450 与肺癌风险和预后之间的牢固关联，并提出了这种功能性拷贝数变异作为对肺癌易感性和预后的潜在生物标志物。
