Key Genes of Peripheral Blood Mononuclear Cells in Hepatocellular Carcinoma and Effective Chinese Herbs： A Bioinformatics Analysis and Systematic Review / 中国实验方剂学杂志

Objective:To explore the key gens of peripheral blood mononuclear cells in hepatocellular carcinoma（HCC-PBMC） and potentially effective Chinese herbs based on bioinformatics， and to verify the clinical efficacy of these Chinese herbs via a systematic review. Method:The chips GSE58208 and GSE36076 of HCC-PBMC were downloaded from the Gene Expression Omnibus （GEO）， followed by the identification of differentially expressed genes （DEGs） using RStudio. After protein-protein interaction （PPI） analysis by STRING， the DAVID was employed for gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. The DEGs of HCC-PBMC were visualized by Cytoscape. The key genes of HCC-PBMC were calculated by CytoHubba plug-in and mapped with those in Coremine Medical for screening out the potential Chinese herbs for the treatment of HCC， which were then included for subsequent systematic review. Result:A total of 203 DEGs were obtained （194 up-regulated and nine down-regulated）. As revealed by DAVID analysis， the DEGs were mainly enriched in such biological processes and signaling pathways as transcriptional regulation of DNA template， hydrolysis of ribonucleic acid phosphodiester bond， positive regulation of intranuclear mitosis and division， skeletal muscle fiber development， activation of mitogen-activated protein kinase（MAPK）activity， Fanconi anemia pathway， and metabolic pathway. The key genes of HCC-PBMC were calculated by Cytoscape to be<italic> </italic>GTPase IMAP family member 1 （GIMAP1）， GTPase IMAP family member 4 （GIMAP4）， GTPase IMAP family member 6 （GIMAP6）， GTPase IMAP family member 7 （GIMAP7）， GTPase IMAP family member 8 （GIMAP8）， interleukin-1<italic>β </italic>（IL-1<italic>β）</italic>， CX3C chemokine receptor 1 （CX3CR1）， C-C chemokine receptor type 2 （CCR2）， Toll-like receptor 7（TLR7）， and epidermal growth factor（EGF）. Through Coremine Medical analysis， it was concluded that Ginseng Radix et Rhizoma， Curcumae Longae Rhizoma， Centellae Herba， and Hedyotidis Herba were closely related to the key genes. Ginseng Radix et Rhizoma has the effects of tonifying and benefiting lung and spleen and enhancing strength， suitable for the liver depression and spleen deficiency syndrome or Qi-Yin deficiency syndrome of HCC. Hence， Si Junzitang with Ginseng Radix et Rhizoma as the sovereign medicinal was included for systematic review. It has been confirmed that Ginseng Radix Et Rhizoma was superior to western medicine alone in improving the overall clinical efficacy， alleviating TCM syndrome， elevating serum CD4⁺and CD4⁺/CD8⁺levels， and reducing the serum CD8⁺and TBIL levels （<italic>P</italic><0.01）， with high safety. Conclusion:This study conducted at the gene level has provided new ideas for clinical diagnosis and treatment of HCC. The systematic review of Ginseng Radix Et Rhizoma against HCC provides a basis for the clinical prevention and treatment of HCC with TCM.