KEY TAKEAWAYS
- The study aimed to identify circulating proteins causally linked to MM and NMSC traits using a multicenter MR framework.
- Researchers identified 13 proteins through MR for BCC, 2 for SCC, and 1 for MM, confirmed by replication.
Skin cancer is the 5th most common cancer type and rates are predicted to rise sharply over the next 20 years. Malignant melanoma (MM) is highly invasive and metastatic and accounts for around 75% of skin cancer-related deaths while non-melanoma skin cancer (NMSC) develops from the epidermis.
It is considered curable at an early stage, although the identification of novel drugs, clinical success, and drug resistance present challenges.
Yajia Li and the team aimed to identify circulating proteins causally linked to MM and NMSC traits using a multicenter Mendelian randomization (MR) framework.
Researchers used large-scale cis-MR to estimate the impact of numerous plasma proteins on MM, NMSC, SCC, and BCC. To ensure robustness, additional analyses like MR Steiger and Bayesian colocalization were conducted.
Subsequently the replication was conducted through meta-analysis. The associations between identified proteins and outcomes are also validated at the tissue level using Transcriptome-Wide Association Study methods.
Furthermore, a protein-protein interaction analysis is conducted to explore the relationship between identified proteins and existing cancer medication targets.
The MR analysis identified associations of 13 plasma proteins with BCC, 2 with SCC, and 1 with MM. Specifically, ASIP and KRT5 are associated with BCC, with ASIP also potentially targeting MM. CTSS and TNFSF8 are identified as promising druggability candidates for BCC. This multidimensional approach nominates ASIP, KRT5, CTSS, and TNFSF8 as potential diagnostic and therapeutic targets for skin cancers.
The MR analyses concluded that there were 13 plasma proteins associated with BCC, 2 with SCC, and one with MM which were confirmed by sensitivity and replication analyses of independent data sets.
The study was supported by the National Key R&D Program of China [No. 2019YFA0112100].
Source: https://pubmed.ncbi.nlm.nih.gov/39003418/
Li Y, Li Q, Cao Z, et al. (2024). “Multicenter proteome-wide Mendelian randomization study identifies causal plasma proteins in melanoma and non-melanoma skin cancers.” Commun Biol. 2024 Jul 13;7(1):857. doi: 10.1038/s42003-024-06538-2. PMID: 39003418; PMCID: PMC11246481.
