Genomic Fabric Remodeling in Prostate Cancer. Genomic Fabric Remodeling in Prostate Cancer

Prostate cancer is a leading cause of death among men but its genomic characterization and best therapeutic strategy are still under debate. The Genomic Fabric Paradigm (GFP) considers the transcriptome as a multi-dimensional mathematical object subjected to a dynamic set of expres-sion correlations among the genes. Here, GFP is applied to gene expression profiles of three (one primary, and two secondary) cancer nodules and the surrounding normal tissue from a surgically removed prostate tumor. GFP was used to determine the regulation and rewiring of the P53 signaling, apoptosis, prostate cancer and several other pathways involved in survival and pro-liferation of the cancer cells. Genes responsible for the block of differentiation, evading apoptosis, immortality, insensitivity to anti-growth signals, proliferation, resistance to chemotherapy and sustained angiogenesis were found as differently regulated in the three cancer nodules with re-spect to the normal tissue. The analysis indicates that even histo-pathologically equally graded cancer nodules from the same tumor have substantially different transcriptomic organizations, raising legitimate questions about the validity of meta-analyses comparing large populations of healthy and cancer humans. The study suggests that GFP may provide a personalized alternative to the biomarkers’ approach of cancer genomics. Overall design: Gene expressions were profiled in two equally graded (Gleason score 4+4=8/10) cancer nodules from a surgically removed prostate cancer Please note that [1] multiple yellow strategy was used to hybridize differently labelleld biological replicas with the microarray and then iteratively normalizing the expression data to the intra-array and inter-array median expression until the maximum error of estimate becomes less than 5% [2] Each raw data file contains raw data for two samples as indicated in the corresponding sample description field.