title: A systems biology-based gene expression classifier of glioblastoma predicts survival with solid tumors.
abstract: Accurate prediction of survival of cancer patients is still a key open problem in clinical research. Recently, many large-scale gene expression clusterings have identified sets of genes reportedly predictive of prognosis; however, those gene sets shared few genes in common and were poorly validated using independent data. We have developed a systems biology-based approach by using either combined gene sets and the protein interaction network (Method A) or the protein network alone (Method B) to identify common prognostic genes based on microarray gene expression data of glioblastoma multiforme and compared with differential gene expression clustering (Method C). Validations of prediction performance show that the 23-prognostic gene classifier identified by Method A outperforms other gene classifiers identified by Methods B and C or previously reported for gliomas on 17 of 20 independent sample cohorts across five tumor types. We also find that among the 23 genes are 21 related to cellular proliferation and two related to response to stress/immune response. We further find that the increased expression of the 21 genes and the decreased expression of the other two genes are associated with poorer survival, which is supportive with the notion that cellular proliferation and immune response contribute to a significant portion of predictive power of prognostic classifiers. Our results demonstrate that the systems biology-based approach enables to identify common survival-associated genes.
authors.affiliation: LIAMA Center for Computational Medicine, National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, the People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.forename: Xingpeng
authors.initials: X
authors.lastname: Jiang
authors.forename: Huizhi
authors.initials: H
authors.lastname: Zhao
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
authors.forename: Zhenjie
authors.initials: Z
authors.lastname: Fan
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Tianzi
authors.initials: T
authors.lastname: Jiang
authors.forename: Sonya Wei
authors.initials: SW
authors.lastname: Song
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics / Q000503:physiopathology*; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D016019:Survival Analysis; D049490:Systems Biology