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Gastric cancer (GC) currently ranks as the fourth leading cause of cancer-related deaths worldwide. Genetic variations may influence GC by regulating genes. The aim of this study was to find pleiotropic genes associated with GC risk. Methods: Summary data-based Mendelian Randomization (SMR) is employed to identify genetic variations that are associated with the GC. The Gene interaction network of THBS3 was established through GeneMANIA, and the molecular pathogenesis was elucidated by function and gene set enrichment analysis (GSEA). Furthermore, we conducted bioinformatics analysis using TIMER2. 0, TCGA database, and TCIA database to identify the expression signatures, prognosis value, and immune characteristics of the identified gene. SMR analysis of eQTL data from GTEx and CAGE showed that THBS3 showed pleiotropic association with GC risk (CAGE: PSMR = 2. 20E-07, PHEIDI = 0. 061; GTExₛtomach: PSMR = 1. 64E-06, PHEIDI = 0. 069). THBS3 and its related genes primarily function through processes such as Extracellular matrix organization, Signaling by PDGF, and Integrin cell surface interactions. The expression of THBS3 is correlated with survival, clinical features, immune cells, and tumor microenvironment. Patients in the low-expression group had better responses to immunotherapy. Our study suggests that THBS3 may play an important role in the occurrence and prognosis of GC and provides a list of prioritized genes for further research on the underlying mechanisms of GC.
Li et al. (Sun,) studied this question.