Using the theory of coevolution to predict protein-protein interactions in non-small cell lung cancer  

作　　者：Meng Zhang Man-Him Chan Wen-Jian Tu Li-Ran He Chak-Man Lee Miao He 

机构地区：[1]School of Life Sciences,Sun Yat-sen University [2]Department of Architecture,Cardiff University [3]College of Software Technology,South China Agricultural University [4]BEE Xergy Consultant Ltd

出　　处：《Chinese Journal of Cancer》2013年第2期91-98,共8页

基　　金：supported by National Natural Science Foundation of China (No.91130009);Science and Technology Planning Project of Guangdong Province of China(No.2003A3080503)

摘　　要：Systems biology has become an effective approach for understanding the molecular mechanisms underlying the development of lung cancer.In this study,sequences of 100 non-small cell lung cancer (NSCLC)-related proteins were downloaded from the National Center for Biotechnology Information (NCBI) databases.The Theory of Coevolution was then used to build a protein-protein interaction (PPI) network of NSCLC.Adopting the reverse thinking approach,we analyzed the NSCLC proteins one at a time.Fifteen key proteins were identified and categorized into a special protein family F(K),which included Cyclin D1 (CCND1),E-cadherin (CDH1),Cyclin-dependent kinase inhibitor 2A (CDKN2A),chemokine (C-X-C motif) ligand 12 (CXCL12),epidermal growth factor (EGF),epidermal growth factor receptor (EGFR),TNF receptor superfamily,member 6(FAS),FK506 binding protein 12-rapamycin associated protein 1 (FRAP1),O-6-methylguanine-DNA methyltransferase (MGMT),parkinson protein 2,E3 ubiquitin protein ligase (PARK2),phosphatase and tensin homolog (PTEN),calcium channel voltage-dependent alpha 2/delta subunit 2 (CACNA2D2),tubulin beta class I (TUBB),SWI/SNF-related,matrix-associated,actin-dependent regulator of chromatin,subfamily a,member 2 (SMARCA2),and wingless-type MMTV integration site family,member 7A (WNT7A).Seven key nodes of the sub-network were identified,which included PARK2,WNT7A,SMARCA2,FRAP1,CDKN2A,CCND1,and EGFR.The PPI predictions of EGFR-EGF,PARK2-FAS,PTEN-FAS,and CACNA2D2-CDH1 were confirmed experimentally by retrieving the Biological General Repository for Interaction Datasets (BioGRID) and PubMed databases.We proposed that the 7 proteins could serve as potential diagnostic molecular markers for NSCLC.In accordance with the developmental mode of lung cancer established by Sekine et al.,we assumed that the occurrence and development of lung cancer were linked not only to gene loss in the 3p region (WNT7A,3p25) and genetic mutations in the 9p region but also to similar events in the regions of 1p36.2 (FRAP1),6q25.2-q27 (PARK2),and 11Systems biology has become an effective approach for understanding the molecular mechanisms underlying the development of lung cancer. In this study, sequences of 100 non-small cell lung cancer （NSCLC）-related proteins were downloaded from the National Center for Biotechnology Information （NCBI） databases. The Theory of Coevolution was then used to build a protein-protein interaction （PPI） network of NSCLC. Adopting the reverse thinking approach, we analyzed the NSCLC proteins one at a time. Fifteen key proteins were identified and categorized into a special protein family F （K）, which included Cyclin D1 （CCND1）, E-cadherin （CDH1）, Cyclin-dependent kinase inhibitor 2A （CDKN2A）, chemokine （C-X-C motif） ligand 12 （CXCL12）, epidermal growth factor （EGF）, epidermal growth factor receptor （EGFR）, ＂I-NF receptor superfamily, member 6 （FAS）, FK506 binding protein 12-rapamycin associated protein 1 （FRAP1）, O-6-methylguanine-DNA methyltransferase （MGMT）, parkinson protein 2, E3 ubiquitin protein ligase （PARK2）, phosphatase and tensin homolog （PTEN）, calcium channel voltage- dependent alpha 2/delta subunit 2 （CACNA2D2）, tubulin beta class I （TUBB）, SWl/SNF-related, matrix- associated, actin-dependent regulator of chromatin, subfamily a, member 2 （SMARCA2）, and wingless- type MMTV integration site family, member 7A （WNT7A）. Seven key nodes of the sub-network were identified, which included PARK2, WNT7A, SMARCA2, FRAP1, CDKN2A, CCND1, and EGFR. The PPI predictions of EGFR-EGF, PARK2-FAS, PTEN-FAS, and CACNA2D2-CDH1 were confirmed experimentally by retrieving the Biological General Repository for Interaction Datasets （BioGRID） and PubMed databases. We proposed that the 7 proteins could serve as potential diagnostic molecular markers for NSCLC. In accordance with the developmental mode of lung cancer established by Sekine et aL, we assumed that the occurrence and development of lung cancer were linked not only to gene loss in the 3p region �

关 键 词：蛋白质相互作用 非小细胞肺癌 理论预测 协同进化 表皮生长因子受体 细胞周期蛋白D1 DNA甲基转移酶 系统生物学 

分 类 号：R734.2[医药卫生—肿瘤]