A Personalized Genomics Approach of the Prostate Cancer.
Decades of research identified genomic similarities among prostate cancer patients and proposed general solutions for diagnostic and treatments. However, each human is a dynamic unique with never repeatable transcriptomic topology and no gene therapy is good for everybody. Therefore, we propose the Genomic Fabric Paradigm (GFP) as a personalized alternative to the biomarkers approach. Here, GFP is applied to three (one primary-"A", and two secondary-"B" & "C") cancer nodules and the surrounding normal tissue ("N") from a surgically removed prostate tumor. GFP proved for the first time that, in addition to the expression levels, cancer alters also the cellular control of the gene expression fluctuations and remodels their networking. Substantial differences among the profiled regions were found in the pathways of P53-signaling, apoptosis, prostate cancer, block of differentiation, evading apoptosis, immortality, insensitivity to anti-growth signals, proliferation, resistance to chemotherapy, and sustained angiogenesis. ENTPD2, AP5M1 BAIAP2L1, and TOR1A were identified as the master regulators of the "A", "B", "C", and "N" regions, and potential consequences of ENTPD2 manipulation were analyzed. The study shows that GFP can fully characterize the transcriptomic complexity of a heterogeneous prostate tumor and identify the most influential genes in each cancer nodule.
['Iacobas|Sanda|S|', 'Iacobas|Dumitru A|DA|0000-0001-9700-6537']
D000368:Aged D017209:Apoptosis D049109:Cell Proliferation D002470:Cell Survival D015972:Gene Expression Regulation, Neoplastic D053263:Gene Regulatory Networks D052138:Genes, Neoplasm D015316:Genetic Therapy D023281:Genomics D006801:Humans D008297:Male D057285:Precision Medicine D011471:Prostatic Neoplasms D015398:Signal Transduction D016159:Tumor Suppressor Protein p53
genomic fabric apoptosis evading apoptosis immortality proliferation ENTPD2 P53 signaling gene master regulators tumor heterogeneity