Research On The Mechanism Of Liuwei Dihuang Pill In Improving The Survival Of Gastric Cancer Patients Based On Bioinformatics

Objective:In recent years,Liuwei Dihuang pill has shown good efficacy in preventing and treating malignant tumors such as lung cancer,liver cancer,and esophageal cancer in the clinical studies.However,there is limited research on the effects of Liuwei Dihuang pill on gastric cancer(GC),and the mechanism of prolonging the survival time of gastric cancer patients is still unclear.Therefore,this study aims to explore the improvement effect of compound Liuwei Dihuang pill on the survival mechanism of gastric cancer patients.Methods:Differential analysis was performed on genes,miRNAs,and lncRNAs from 32 normal samples and 375 cases of gastric cancer transcriptome samples(RNA-seq)from the Cancer Genome Atlas(TCGA)database using DESeq2 and edgeR algorithms.An lncRNA-miRNA-gene ceRNA regulatory network was established using databases like miRcode.Key genes related to the prognosis of gastric cancer patients were screened using weighted gene co-expression network analysis(WGCNA).A survival prognosis model was established using clinical data.The active ingredients and corresponding targets of Liuwei Dihuang pill were retrieved from databases such as the Traditional Chinese Medicine Systems Pharmacology(TCMSP)database.A volcano plot was used to analyze the potential therapeutic targets of Liuwei Dihuang pill for GC by comparing its active ingredient targets with GC-related genes.A targeted disease network of Liuwei Dihuang pill was constructed using Cytoscape software.Gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed on the obtained targets.Ligands and core compounds were docked using AutoDock and PyMol software,and the binding activity between components and targets was evaluated by docking scores.Finally,AutoDock software was used to verify the molecular docking between drug components and core targets in the network.Results:1.A total of 2920 common genes,8 common miRNAs,and 869 common lncRNAs were found to be differentially expressed between normal and gastric cancer samples,and a regulatory network was constructed based on this.The module with the highest correlation with patient survival time was found through WGCNA.The survival model of AL035610.1,DCLK3,DNASE1L3,PRSS30P,and TAC3 had significant differences between high-risk and low-risk groups.2.Liuwei Dihuang pill had 69 active ingredients and 172 potential targets.The related targets of GC were 892 and the key targets were 15.GO enrichment analysis showed that Liuwei Dihuang pill may exert its anti-gastric cancer effects through cell toxicity,oxidative stress,metabolism,and apoptosis functions.KEGG pathway enrichment analysis identified 3 related signal pathways,gastric cancer signal pathway,Toll-like receptor signal pathway and IL-17 signal pathway,with Toll-like receptor signal pathway being the most enriched,followed by IL-17 signal pathway.Molecular docking results showed that the main active ingredients of Liuwei Dihuang pill had relatively stable binding activity with core targets.Conclusion:The regulatory network primarily composed of miR508,miR372,and miR184 plays a crucial role in the occurrence and development of gastric cancer.The survival model constructed with AL035610.1,DCLK3,DNASE1L3,PRSS30P,and TAC3 can effectively predict the prognosis of gastric cancer patients.Liuwei Dihuang Pill exerts its anti-gastric cancer effects through effective ingredients such as quercetin,naringenin,huperzine A,and tetrahydropalmatine,targeting genes like CXCL10,CXCL8,SPP1,and MPP3,affecting gastric cancer signaling pathway,Toll-like receptor signaling pathway,and IL-17 signaling pathway,thereby promoting cell toxicity,oxidative stress,metabolism,and apoptosis functionally.