Pathway-based Analysis of the Hidden Genetic Heterogeneities in Cancers

查看全文 作　　者：Xiaolei [1]Zhao;Shouqiang [2]Zhong;Xiaoyu [3]Zuo;Meihua [1]Lin;Jiheng [1]Qin;Yizhao [1]Luan;Naizun [2]Zhang;Yan [2]Liang;Shaoqi [1,3]Rao 机构地区：[1]Institute for Medical Systems Biology and Department of Medical Statistics and Epidemiology,School of Public Health,Guangdong Medical College;[2]Maoming People’s Hospital;[3]Department of Medical Statistics and Epidemiology,School of Public Health,Sun Yat-Sen University 出　　处：《Genomics, Proteomics & Bioinformatics》索引2014年第12卷第1期,共8页 基　　金：supported in part by the National Natural Science Foundation of China(Grant Nos.31071166 and 81373085);Natural Science Foundation of Guangdong Province,China(Grant No.8251008901000007);Science and Technology Planning Project of Guangdong Province(Grant No.2009A030301004);Science and Technology Project of Dongguan(Grant No.2011108101015);the funds from Guangdong Medical College(Grant Nos.XG1001,JB1214,XZ1105,STIF201122,M2011024 and M2011010) 摘　　要：Many cancers apparently showing similar phenotypes are actually distinct at the molecular level,leading to very different responses to the same treatment.It has been recently demonstrated that pathway-based approaches are robust and reliable for genetic analysis of cancers.Nevertheless,it remains unclear whether such function-based approaches are useful in deciphering molecular heterogeneities in cancers.Therefore,we aimed to test this possibility in the present study.First,we used a NCI60 dataset to validate the ability of pathways to correctly partition samples.Next,we applied the proposed method to identify the hidden subtypes in diffuse large B-cell lymphoma(DLBCL).Finally,the clinical significance of the identified subtypes was verified using survival analysis.For the NCI60 dataset,we achieved highly accurate partitions that best fit the clinical cancer phenotypes.Subsequently,for a DLBCL dataset,we identified three hidden subtypes that showed very different 10-year overall survival rates(90%,46% and 20%) and were highly significantly(P = 0.008) correlated with the clinical survival rate.This study demonstrated that the pathwaybased approach is promising for unveiling genetic heterogeneities in complex human diseases. 关 键 词：遗传异质性 癌症 基础 隐藏 B细胞淋巴瘤 临床意义 分子水平 数据集