Proteome-wide Mendelian randomization and colocalization analysis identify therapeutic targets for cutaneous melanoma

Cutaneous melanoma (CM) is the deadliest form of skin cancer, posing a significant threat to human health. In the ongoing efforts to develop effective treatments, identifying novel therapeutic targets is crucial. This research aimed to use Mendelian randomization and colocalization analysis to discover plasma proteins that could serve as new therapeutic targets for CM, while also assessing the potential adverse effects associated with these targets. The study harnessed plasma protein data from the UK Biobank Pharmaceutical Proteomics Project database, which contained genome-wide association data for 2940 proteins. These data were integrated with CM data from the Finnish database, involving 3194 patients and 314,193 controls. Proteome-wide analysis was then conducted to explore the associations between plasma proteins and CM risk. Through the proteome-wide analysis, 2 proteins, tyrosinase-related protein 1 and dipeptidase 1, were identified to have significant associations with CM risk. Notably, dipeptidase 1 exhibited an inverse relationship with CM risk, indicating its potential as a therapeutic target. However, the findings also raised concerns about its possible link to dementia. This comprehensive research approach successfully illuminated the causal relationships between specific plasma proteins and CM. It not only identified potential therapeutic targets but also emphasized the importance of understanding the broader implications of targeting these proteins, including potential adverse effects. The results lay the groundwork for further exploration of personalized treatment strategies for CM.