Bioinformatics-based study of the immune microenvironment of gastric precancerous lesions and prediction and validation of potential traditional Chinese medicine

OBJECTIVE: To analyse the key genes and immune cell infiltration in chronic gastritis (CG), precancerous gastric lesion (PLGC), and early gastric cancer (EGC), and to explore the potential therapeutic targets and traditional Chinese medicine (TCM) therapeutic strategies. METHODS: (1) Transcriptome microarray datasets of CG, PLGC and EGC patients were collected from the GEO database, R language was used to screen out differentially expressed genes (DEGs) and enriched for analysis, PPI network was constructed, key genes were identified by Cytoscape, and immune cell infiltration was analysed by Timer2.0 and CIBERSORT algorithms. (2) GEPIA2 database was used to clinically validate the expression levels of key genes, and cBioPortal to analyse gene mutations. (3) Prediction of therapeutic herbs and regulatory networks based on Coremine Medical and TCMSP databases. (4) Validation based on in vitro experiments. RESULTS: (1) PLGC-related DEGs were associated with immune-related biological processes and pathways such as Th17 cell differentiation, and the core genes were related to the regulation and promotion of signaling, activation, migration, adhesion and immune response of immune cells. (2) Immune cell infiltration analysis of M1 macrophages and initial CD4+ T cell infiltration scores were significantly different (P < 0.05). (3) PTPRC, IFNG, CD19, CCR7, ITGAM, CD69, IL7R, CD27, ITGAX, and CXCR4 are the key genes of gastric mucosal "inflammation-cancer" transformation, and there is a significant difference between the expression levels of gastric cancer tissues and normal tissues. (4) Predicting the potential targets of Chinese medicines, the four qi of Chinese medicines are mainly cold, cool, and flat; the five flavours are mainly pungent, bitter, and sweet; the meridians are mostly spleen, liver, lung, and kidney meridians; and the effects are clearing heat and removing toxins, dispelling dampness, and resolving turbidities, which have revealed the components and targets of Chinese medicines that may be effective in the treatment of PLGCs and EGCs. (5) Hua-zhuo-Jie-du prescription optimized based on the theory of Zhuo-Du and the prediction results of TCM can effectively regulate the polarization of macrophages and improve the immune microenvironment to treat PLGC.(6) Conclusion: Changes in the immune microenvironment play an important role in the progression of PLGC, and the traditional Chinese medicines of clearing heat and removing toxins and dispelling dampness and resolving turbidities are important for the prevention and treatment of gastric cancer and the reversal of gastric inflammation-cancer transformation in the gastric mucosa.