Gene Expression: Protein Interaction Systems Network Modeling Identifies Transformation-Associated Molecules and Pathways in Ovarian Cancer

Abstract

Multiple, dissimilar genetic defects in cancers of the same origin contribute to heterogeneity in tumor phenotypes and therapeutic responses of patients, yet the associated molecular mechanisms remain elusive. Here, we show at the systems level that serous ovarian carcinoma is marked by the activation of interconnected modules associated with a specific gene set that was derived from three independent tumor-specific gene expression data sets. Network prediction algorithms combined with preestablished protein interaction networks and known functionalities affirmed the importance of genes associated with ovarian cancer as predictive biomarkers, besides "discovering" novel ones purely on the basis of interconnectivity, whose precise involvement remains to be investigated. Copy number alterations and aberrant epigenetic regulation were identified and validated as significant influences on gene expression. More importantly, three functional modules centering on c-Myc activation, altered retinoblastoma signaling, and p53/cell cycle/DNA damage repair pathways have been identified for their involvement in transformation-associated events. Further studies will assign significance to and aid the design of a panel of specific markers predictive of individual-and tumorspecific pathways. In the parlance of this emerging field, such networks of gene-hub interactions may define personalized therapeutic decisions.

Evaluation of Epigenetic Drug Targeting of Heterogenous Tumor Cell Fractions Using Potential Biomarkers of Response in Ovarian Cancer

“…In the current study, we identified epigenetic dysregulation of cellular functions that complement aberrant gene and protein expression patterns in our experimental model that recapitulates disease progression (25,29,31,40). Querying the clinical relevance of these epigenetic changes with tumors in the TCGA database revealed a small number of biomarker genes potentially associated with transformation (refs.…”

“…For immunoprecipitation, 4 mg of sonicated DNA was incubated for 12 hours at 4 C with anti-5-methylcytosine/K4/K9/K27 monoclonal antibody; standard protocols were followed for further enrichment and hybridization (31). Genome-wide promoter methylation profiling was performed using Agilent Human Promoter CpG 244 k Array (G4492A).…”

“…Genome-wide promoter methylation profiling was performed using Agilent Human Promoter CpG 244 k Array (G4492A). Agilent Human Promoter CoC 244 k (G4489A) was used for histone methylation (31). MeDIP-chip (promoter DNA methylation) or ChIP-on-ChIP (histone methylation) data analysis was performed with Agilent genomic workbench.…”

STEM CELL AND CANCER STEM CELL: A Tale of Two Cells

“…In addition to their ability to self-renew and Interestingly, in serum free media, sometimes CSC can differentiate into progenitor cells (House et al, 2015). A.Common features found in normal and cancer stem cells (Bapat et al, 2010) 01 Capacity for asymmetric divisions (self-renewal) thatproduces a quiescent stem cell and a dedicated progenitor and plays important role toward emerging a dangerous cell mass.…”

Clinical Implementation of Metabolomics

“…Most studies currently remain focused on local level networks within a set of related genes or protein expressions (Bapat et al, 2010;Kirouac et al, 2010). Yet a combination of different levels of networks can be connected to overview the whole system.…”