Biologia Molecular: Acesso Aberto

ALK Folic Acid Transport and Integrin Signal Induced-Angiogenesis Network in Human Hepatocellular Carcinoma (HCC) by Systems-Theoretical Analysis

Abstract

Lin Wang, Juxiang Huang and Hong Lin

We constructed the high-expression ALK activated transport and signal network in human hepatocellular carcinoma (HCC) compared with low-expression (fold change ≥2) no-tumor hepatitis/cirrhotic tissues (HBV or HCV infection) in GEO data set, by using integration of gene regulatory activated and inhibited network inference method with gene ontology (GO) analysis. Our result showed that ALK transport and signal upstream network ECT2, FOLR1, GNAZ, GRM1, ITGA2, LEF1, NR5A1, PTHLH, RIMS3, SORT1, SOX2 activated ALK, and downstream ALK-activated BAP1, CAD, CDH13, CNTNAP2, GRM1, ITGA2, LAPTM4B, MAP2K6, NR5A1, STMN1 in HCC. We obtained that the different biological processes of ALK activated network consisted of folic acid transport, cell surface receptor linked signal transduction, cell-cell signaling, G-protein coupled receptor protein signaling pathway, integrin-mediated signaling pathway, intracellular signaling cascade, low density lipoprotein mediated signaling, Rac protein signal transduction, Rho protein signal transduction in HCC compared with the activated network of no-tumor hepatitis/cirrhotic tissues, as a result of inducing folic acid transport and integrin signal induced-angiogenesis in HCC. Our hypothesis was verified by the different and the same biological processes of ALK activated transport and signal network of HCC compared with the corresponding inhibited network of no-tumor hepatitis/cirrhotic tissues and HCC, respectively.