Identifying THBS3 as a potentially viable therapeutic target for gastric cancer: Intergration of Mendelian...

Although targeted therapy significantly improves the prognosis of gastric cancer patients, the availability of cancer targeted drugs in clinical practice is still limited. In order to identify potential therapeutic targets for gastric cancer, Mendelian randomization (MR) analysis based on aggregated data was conducted. Specifically, cis eQTL data were obtained from the whole blood and gastric cohorts of GTEx Consortium V8 as exposure variables. Obtain cancer summary statistical data representing outcome variables from the FinnGen database. Using co localization analysis to evaluate whether common single nucleotide polymorphisms (SNPs) are associated with cancer risk and gene expression. Ultimately, thrombospondin-3(THBS3) was identified as a significant gene in both cohorts, supported by consistent colocalization evidence. Subsequently, a dual sample MR analysis was conducted to investigate the correlation between gene expression and gastric cancer risk, and the results also confirmed the relationship between THBS3 gene expression and gastric cance risk. In addition, a meta-analysis was conducted showing that THBS3 is a gene with poor cancer prognosis. Cell studies indicate that inhibiting THBS3 expression can reduce cell proliferation, enhance sensitivity to gastric cancer-related drugs, and lower MVP gene expression may linked to drug resistance. It also influences tumor growth signaling, metabolic pathways, and cell adhesion processes. In summary, based on the research results of SMR, colocalization, dual sample MR, meta-analysis, and other analysis methods, there is convincing evidence to support the view that THBS3 has important prospects as a feasible therapeutic target gene for cancer.