Identification of key genes of gastric cancer and active components of traditional Chinese medicine based on bioinformatics and network pharmacology
Objective:Thntais study aims to explore key genes that drive the progression of gastric cancer through bioinformatics,and screening potential active ingredients of traditional Chinese medicine combined with network pharmacological analysis,with a prospect of providing basis for the prevention and treatment of gastric cancer.Methods:The gene expression profile chip(GSE191275)was downloaded from the GEO database of NCBI,and the differentially expressed genes(DEGs)of gastric cancer experimental group VS intestinal metaplasia group and intestinal metaplasia VS non-atrophic gastritis were screened by GEO2R,and the genes with the same change pattem in the process of"non-atrophic gastritis-intestinal metaplasia-gastric cancer"were searched by Venn diagram.The interaction network of proteins was constructed by STRING database,and key genes were screened by CytoScape.ROC curve analysis was used to further screen potential targets for gastric cancer treatment.Potential active ingredients of Chinese medicine were extracted from TCMSP.A total of 40 patients with gastric cancer prelesions admitted to the Outpatient Department of Spleen and Stomach,Xiamen Hospital of Traditional Chinese Medicine were included as the study subjects,and the patients were divided into the routine control group and the quercetin supplement group according to random number table method,with 20 cases in each group.The therapeutic effect,serological indexes,target inhibition and adverse reactions in the two groups were observed.Results:A total of 49 continuously up-regulated and 39 continuously down-regulated genes during the course of gastric cancer were identified.Through double screening and identification,PCSKl,PTGS2,MMP3 and CCL20 were identified as potential gene targets for the prevention and treatment of gastric cancer.Quercetin was identified as a dual inhibitor of PTGS2/MMP3 after a number of screening rules for potential TCM active ingredients targeted by TCMSP.The clinical observation confirmed that quercetin supplementation significantly improved the total effective rate of the conventional treatment,the difference was statistically significant(P＜0.05).Quercetin supplementation also significantly down-regulated the levels of serum COX-2 and p53,and the expressions of PTGS2 and MMP3 mRNA in gastric mucosa(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:This study identifies PCSK1,PTGS2,MMP3,and CCL20 as key genes in the"non-atrophic gastritis-intestinal metaplasia-gastric cancer"process,and that the targeted inhibition of PTGS2/MMP3 by quercetin is expected to be clinically applied in the prevention and treatment of gastric cancer.
Gastric cancerBioinformaticsKey geneNetwork pharmacologyActive ingredient of Chinese medicine
万方数据
维普
