A genetic perspective on the relationship between circulating proteins and bladder cancer: a study from drug-targeted Mendelian randomization

Abstract

Abstract Background: Bladder cancer is one of the most common tumor in men worldwide, and advanced bladder cancer has a high incidence and mortality rate. The treatment of bladder cancer is currently developing slowly, and there is an urgent need for effective therapies to improve the survival of patients with bladder cancer. Method:We firstly analyzed the bladder cancer database from biobank and circulating proteins by mendelian(MR).The results were co-localized after FDR correction, and we selected PPH4>0.8 as the protein with strong evidence.We used a bladder cancer database from Finland as a validation set, which was similarly subjected to MR analysis of its results. Result:In the first step we performed a two-sample MR analysis of circulating proteins and the bladder cancer database from UKB, screened 46 proteins with P<0.05 by FDR test, and co-localized proteins in the results were analyzed. In the second step we again performed MR analysis on circulating proteins and the bladder cancer data from the Finnish database, which were also subjected to FDR test and screened for proteins with P<0.05, and combined the FDR test results with the bladder cancer data.We compared the co-localized proteins from UKB with the results obtained from the Finnish database, and a total of 7 proteins were found to be validated. Conclusion: GSTM1, GSTM3, GSTM4, ASIP, CSF2RB, CNDP1, and DLK1 deserve to be explored for their druggability, and we look forward to more antitumor drugs to treat bladder cancer in the future.