Pathway-based Analysis of the Hidden Genetic Heterogeneities in Cancers

作     者：Xiaolei Zhao Shouqiang Zhong Xiaoyu Zuo Meihua Lin Jiheng Qin Yizhao Luan Naizun Zhang Yan Liang Shaoqi Rao 

作者机构：Institute for Medical Systems Biology and Department of Medical Statistics and EpidemiologySchool of Public HealthGuangdong Medical College Maoming People’s Hospital Department of Medical Statistics and EpidemiologySchool of Public HealthSun Yat-Sen University 

出 版 物：《Genomics, Proteomics & Bioinformatics》 (基因组蛋白质组与生物信息学报（英文版）)

年 卷 期：2014年第12卷第1期

页      面：31-38页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 0714[理学-统计学（可授理学、经济学学位）] 0703[理学-化学] 100214[医学-肿瘤学] 0701[理学-数学] 0812[工学-计算机科学与技术（可授工学、理学学位）] 10[医学] 

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) 

主　　题：Genetic heterogeneity Pathway-based approach Sample partitioning Enrichment analysis Survival analysis Cancer 

摘      要：Many cancers apparently showing similar phenotypes are actually distinct at the molecular level,leading to very different responses to the same *** has been recently demonstrated that pathway-based approaches are robust and reliable for genetic analysis of ***,it remains unclear whether such function-based approaches are useful in deciphering molecular heterogeneities in ***,we aimed to test this possibility in the present ***,we used a NCI60 dataset to validate the ability of pathways to correctly partition ***,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 *** the NCI60 dataset,we achieved highly accurate partitions that best fit the clinical cancer ***,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 *** study demonstrated that the pathwaybased approach is promising for unveiling genetic heterogeneities in complex human diseases.