AFP, RRM2, NUSAP1,ACTN2 Computational Functional Network Construction And Analysis In No-Tumor Hepatitis/Cirrhotic Liver Tissues And HCC

Based on integrated gene regulatory network infer method by linear programming and a decomposition procedure with analysis of the significant function cluster using kappa statistics and fuzzy heuristic clustering from the database for annotation visualization and integrated discovery, we constructed and analyzed significant higher expression gene AFP, RRM2, NUSAP1, ACTN2 activated & inhibited functional network from HCC vs no-tumor hepatitis/cirrhosis pateints in GEO Dataset. We have successfully applied this method to gene data analysis, and made breakthroughs in our studies of AFP secreted network, RRM2 phosphoprotein network in HCC and TNFRSF11B development network, CREB5 regulation network, MYBPC1 phosphoprotein network and IFI27 network in frontal cortex of HIV encephalitis.In this study, our study proved that in AFP secreted network, we gained negative result of AFP secreted module and predicted decrease of AFP secreted module in HCC. Importantly, we datamined that AFP secreted cluster of HCC was involved in disease mutation (only in experiment) without cell surface receptor linked signal transduction, neuroactive ligand-receptor interaction, cell-cell signaling and pancreas (only in control), the condition was vital to invasion of HCC. Our result revealed that common terms in both control and experiment included secreted, extracellular region, extracellular region part, extracellular space, signal peptide, signal, disulfide bond, glycosylation site:N-linked (GlcNAc...) and glycoprotein, and these terms were less relative to invasion, therefore we deduced weaker AFP secreted network in HCC (published in SCI-indexed international academic journal, Tumor Biology). In RRM2 phosphoprotein network, we obtained negative result of RRM2 phosphoprotein module and predicted decrease of RRM2 phosphoprotein module in HCC. Otherwise, our integrative result showed that RRM2 phosphoprotein of HCC contained common terms of phosphoprotein and cell cycle, particular terms of cell-cell signaling, cell projection part, glycoprotein, cell projection, cell adhesion, biological adhesion, integral to plasma membrane, plasma membrane, kinase and phosphorus metabolic process, and no terms of cell death and ion binding compared with no-tumor hepatitis/cirrhotic liver tissues, all the condition was vital to invasion of HCC. Therefore, we deduced weaker RRM2 phosphoprotein function in HCC (published in SCI-indexed international academic journal, Cellular Physiology and Biochemistry). In NUSAP1 cell cycle network, we acquired positive result of NUSAP1 cell cycle module and predicted increase of NUSAP1 cell cycle module in HCC. We datamined that NUSAP1 cell cycle cluster of HCC was involved in cell cycle checkpoint and regulation of phosphorylation (only in experiment) without disease mutation and transcription (only in control), the condition was vital to proliferation of HCC. Our result demonstrated that common terms in both control and experiment included cell cycle, phosphoprotein, intracellular non-membrane-bounded organelle, acetylation and ubl conjugation, and these terms were more relative to proliferation, therefore we deduced stronger NUSAP1 cell cycle network in HCC. In ACTN2 non-membrane-bounded organelle network, we got negative result of ACTN2 non-membrane-bounded organelle module and predicted decrease of ACTN2 non-membrane-bounded organelle module in HCC. Importantly, we datamined that ACTN2 non-membrane-bounded organelle cluster of HCC was involved in positive regulation of cell cycle, DNA damage and phosphorus metabolic process (only in experiment) without plasma membrane (only in control), the condition was vital to proliferation and cell death of HCC. Our result demonstrated that common terms in both control and experiment included non-membrane-bounded organelle, cell cycle, regulation of cell cycle, negative regulation of molecular function, cytoskeleton, kinase, ubl conjugation, phosphoprotein, ATP binding, macromolecule catabolic process, zinc ion binding and cell death, and these terms were more relative to proliferation and cell death, therefore we deduced weaker ACTN2 non-membrane-bounded organelle network in HCC.