title: Systems biology approach to studying proliferation-dependent prognostic subnetworks in breast cancer.
abstract: Tumor proliferative capacity is a major biological correlate of breast tumor metastatic potential. In this paper, we developed a systems approach to investigate associations among gene expression patterns, representative protein-protein interactions, and the potential for clinical metastases, to uncover novel survival-related subnetwork signatures as a function of tumor proliferative potential. Based on the statistical associations between gene expression patterns and patient outcomes, we identified three groups of survival prognostic subnetwork signatures (SPNs) corresponding to three proliferation levels. We discovered 8 SPNs in the high proliferation group, 8 SPNs in the intermediate proliferation group, and 6 SPNs in the low proliferation group. We observed little overlap of SPNs between the three proliferation groups. The enrichment analysis revealed that most SPNs were enriched in distinct signaling pathways and biological processes. The SPNs were validated on other cohorts of patients, and delivered high accuracy in the classification of metastatic vs non-metastatic breast tumors. Our findings indicate that certain biological networks underlying breast cancer metastasis differ in a proliferation-dependent manner. These networks, in combination, may form the basis of highly accurate prognostic classification models and may have clinical utility in guiding therapeutic options for patients.
authors.affiliation: 1] Division of Radiology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. [2] School of Mathematical Sciences, Beijing Normal University, Beijing, 100875, P R China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Song
authors.affiliation: Division of Radiology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Mathematical Sciences, Beijing Normal University, Beijing, 100875, P R China.
authors.forename: Jiguang
authors.initials: J
authors.lastname: Bao
authors.affiliation: Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Pullikuth
authors.affiliation: Division of Radiology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: King C
authors.initials: KC
authors.lastname: Li
authors.affiliation: Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
authors.forename: Lance D
authors.initials: LD
authors.lastname: Miller
authors.affiliation: 1] Division of Radiology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. [2] Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000465:Algorithms; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D016208:Databases, Factual; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D060066:Protein Interaction Maps; D059467:Transcriptome