CN43 - Comprehensive pan-cancer exploration of the ubiquitin-proteasome system: A bidirectional Bayesian Weighted Mendelian randomization study

Background

Numerous observational studies have indicated a potential causal association between the ubiquitin-proteasome system (UPS) and the development of tumors. However, the causality of UPS in the development of cancers has yet to be determined.

Methods

We used bidirectional Mendelian randomization(MR) and Bayesian weighted MR(BWMR) to interpret the causal relationship between the 57 ubiquitin proteasome system-related proteins (UPSs) and 23 types of cancers (including different subtypes). For assessing horizontal pleiotropy, the researchers employed MR-Egger regression and MR-PRESSO global tests, with the Cochrane Q-test utilized to appraise the presence of heterogeneity.

Results

After sensitivity analysis, we determined through bidirectional MR that the elevation of 19 UPSs is associated with an increased risk of 14 tumors, while the elevation of 22 ubiquitin-proteasome proteins serves as a protective factor for 14 types of cancers. Reverse MR identified causal associations between 16 types of tumors and 33 UPSs. Finally, we conducted BWMR on positive results from bidirectional MR and found that 21 results were non-significant.

Conclusions

In summary, we explored the causal relationship between the UPS and pan-cancer at the genetic level, laying the foundation for potential drug targets and biomarkers.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Q. Xu.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.