TLR7 regulates tumor microenvironment to influence prognosis of Asian gastric cancer patients

Background and Objective Gastric cancer (GC) is the fifth most common malignant tumor in the world, and Asia has the highest incidence of GC. The tumor microenvironment (TME) and immunogenic cell death (ICD) mechanisms play important roles in the prognosis of patients with GC. In this study, we investigated the relationship between the TME and the prognosis of Asian patients with GC by analyzing data from Asian patients with GC obtained from The Cancer Genome Atlas (TCGA) database and further explored by which mechanism TME affects prognosis. Methods We downloaded the data of Asian GC patients from the TCGA database, scored the TME of each sample, explored the relationship between the score and survival as well as clinical stage, performed differential analysis on stromal cells and immune cells, screened out differential genes (DEGs) and identified the intersections, and performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on the DEGs that intersected and constructed the protein interaction network. Then, we screened ICD-related genes (IRGs) from the intersecting stromal cell- and immune cell-related DEGs, extracted the expression of IRGs, performed differential expression analysis to screen out the differential IRGs, constructed a prognostic model by regression analysis, and verified the accuracy of the model with Kaplan–Meier (K–M) survival curves and receiver operating characteristic (ROC) curves. Results Population survival was lower in the group with high stromal and immune cell content. The higher the clinical stage is, the greater the stromal and immune cell content. There were a total of 1367 upregulated DEGs and 157 downregulated DEGs in the stromal and immune cell high content group, which were highly enriched in some GO and KEGG pathways. There were 29 IRGs in the intersecting stromal cell- and immune cell-related DEGs. There were 19 IRGs that differed between tumor samples and normal samples. Through multifactorial regression analysis, it was found that TLR7 was closely related to patient prognosis, and a new risk score prognostic model was constructed for Asian GC patients based on TLR7. Validation of the model through K‒M survival curves and receiver operating characteristic (ROC) curves proved that the model had certain predictive value. Conclusion TLR7 may regulate the number of stromal and immune cells in the TME of Asian GC patients through ICD-associated mechanisms, thereby affecting patient prognosis.