title: Integrated proteomic, transcriptomic, and biological network analysis of breast carcinoma reveals molecular features of tumorigenesis and clinical relapse.
abstract: Gene and protein expression changes observed with tumorigenesis are often interpreted independently of each other and out of context of biological networks. To address these limitations, this study examined several approaches to integrate transcriptomic and proteomic data with known protein-protein and signaling interactions in estrogen receptor positive (ER+) breast cancer tumors. An approach that built networks from differentially expressed proteins and identified among them networks enriched in differentially expressed genes yielded the greatest success. This method identified a set of genes and proteins linking pathways of cellular stress response, cancer metabolism, and tumor microenvironment. The proposed network underscores several biologically intriguing events not previously studied in the context of ER+ breast cancer, including the overexpression of p38 mitogen-activated protein kinase and the overexpression of poly(ADP-ribose) polymerase 1. A gene-based expression signature biomarker built from this network was significantly predictive of clinical relapse in multiple independent cohorts of ER+ breast cancer patients, even after correcting for standard clinicopathological variables. The results of this study demonstrate the utility and power of an integrated quantitative proteomic, transcriptomic, and network analysis approach to discover robust and clinically meaningful molecular changes in tumors.
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Marcin
authors.initials: M
authors.lastname: Imielinski
authors.forename: Sangwon
authors.initials: S
authors.lastname: Cha
authors.forename: Tomas
authors.initials: T
authors.lastname: Rejtar
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Richardson
authors.forename: Barry L
authors.initials: BL
authors.lastname: Karger
authors.forename: Dennis C
authors.initials: DC
authors.lastname: Sgroi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D044584:Carcinoma, Ductal / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D053208:Kaplan-Meier Estimate; D061346:Laser Capture Microdissection; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D016016:Proportional Hazards Models; D060066:Protein Interaction Maps; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D012372:ROC Curve; D055815:Young Adult
chemical_list: D020543:Proteome