Hemotherapeutic drug like HCC [13]. Moreover, TCM-MESH and TCM-ID have been applied to investigate candidate active ingredients and herbs that might target these hub genes. A network consisting of 3 hub genes (TOP2A, CCNB1, and NUF2), 9 effective compounds, and 40 associated herbs was constructed (Figure 12B). Similarly, TOP2A was putatively targeted by most compounds (three,3′,4′,five,5′,7-hexahydroxyflavone, proanthocyanidin b2, epigallocatechin 3-gallate, howiinol a, and betulic acid). Among all the compounds, proanthocyanidin b2 and plumbagin showed the top two nodes using the highest degrees (proanthocyanidin b2 was contained in 17 herbs and plumbagin was contained in 9 herbs). Proanthocyanidin b2 was well-documented with anticarcinogenic properties via anti-inflammator and antioxidant potential, and was demonstrated to exert anti-tumor efficacy for HCC in vitro and in vivo [14]. Plumbagin was also indicated to suppress HCC carcinogenesis via induction of cell arrest and cellular apoptosis [15]. These data may perhaps shed light upon target therapy for HCV-HCC patients. Comparison with the hub genes and pathways amongst HCV-HCC and HBV-HCC In a prior study, we reported 17 hub genes with diagnostic and prognostic values in HBV-HCC [16]. Interestingly, 3 of them (CCNB1, TOP2A, NEK2) were also identified as vital genes in HCV-HCC, which may to some extent reflect the widespread transcriptome regulatory mechanisms in liver cancer induced by viral hepatitis. We also compared the robust DEGs involving HCV-HCC and HBV-HCC, as the outcome, we found 38 common upregulated DEGs and 95 frequent downregulated DEGs. Notably, commonly critical KEGG pathways enriched by robust DEGs were identified among HCV-HCC and HBV-HCC which includes cell cycle, p53 signaling pathway, oocyte meiosis, progesterone-mediated oocyte maturation, Human T-cell leukemia virus 1 infection, cellular senescence, retinol metabolism, tryptophan metabolism, complement and coagulation cascades, drug metabolism cytochrome P450, tyrosine metabolism (Supplementary Figure 3). Expertise like that may reveal indispensable and important pathways for the total transition from hepatitis to HCC, and for that reason would throw light on thewww.aging-us.comAGINGyielding of doable predictors or biomarkers during the process.DISCUSSIONDespite intense efforts which have been produced for the investigation of HCC pathogenesis and its candidatebiomarker PPARβ/δ Activator web searching, the general prognosis for HCC sufferers was nevertheless unfavorable, along with the comprehensive explanation for its transcriptional and genetic mechanisms remained elusive, particularly for HCV associated HCC. In the current study, 240 robust DEGs of HCV-HCC were, for the first time, screened according to 5 public datasets, including 58 upregulated genes andFigure 12. Network pharmacological analysis to determine candidate drugs and efficient compounds for therapeutic targets of HCV-HCC. (A) Drug-hub gene network identified from the DGIdb. Green nodes indicate the predictive miRNAs and red nodes indicate thetargeted hub genes. (B) Herb-compounds-hub gene network predicted by TCM-MESH and TCM-ID. red nodes indicate hub genes, blue nodes indicate the active compounds and green nodes indicate the putative herbs containing these compounds.www.aging-us.comAGING182 downregulated genes. The upregulated genes mainly participated in cell PI3K Inhibitor drug cycle-associated GO terms, for example cell division, cell cycle phase transition, and spindle. Cell-cycle aberration was considered a hallmark of cancer.
