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Updated: Jun 17, 2025
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Identification of potential therapeutic targets for skin cutaneous melanoma on the basic of transcriptomics
Fengling Shi1,2, Tao Li1,2, Huiling Shi1,2
1Department of Oncology, The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake Hospital, Medical Center of Soochow University, Suzhou, China.
Background:
Advanced skin cutaneous melanoma (SKCM) is responsible for the majority of skin cancer-related deaths. Apart from the rare BRAF V600F mutation, which can be targeted with specific drugs, there are currently no other novel effective therapeutic targets.
Methods:
We used SMR analysis with cis-expressed quantitative trait locus (cis-eQTL) as the exposure variable and SKCM as the outcome variable to identify potential therapeutic targets for SKCM. Colocalization assays and HEIDI tests are used to test whether SKCM risk and gene expression are driven by common SNPs. Replication analysis further validated the findings, and we also constructed protein-protein interaction networks to explore the relationship between the identified genes and known SKCM targets. Drug prediction and molecular docking further validated the medicinal value of drug targets. Transcriptome differential analysis further validated that there were differences between normal tissues and SKCM for the selected targets.
Results:
We identified 13 genes significantly associated with the risk of SKCM, including five protective genes and eight harmful genes. The HEIDI test and co-localization analysis further indicates a causal association between genes (SOX4, MAFF) and SKCM, categorized as Class 1 evidence targets. The remaining 11 genes, except for HELZ2 show a moderately causal association with SKCM, categorized as Class 2 evidence targets. Target druggability predictions from DGIdb suggest that SOX4, MAFF, ACSF3, CDK10, SPG7, and TCF25 are likely to be future drug targets.
Conclusion:
The study provides genetic evidence for targeting available drug genes for the treatment of SKCM.
Insights
This study identifies 13 genes linked to skin cutaneous melanoma (SKCM) risk, offering potential new drug targets. Six genes show promise as therapeutic targets for advanced SKCM treatment.
Area of Science:
- Genomics
- Oncology
- Pharmacology
Background:
- Advanced skin cutaneous melanoma (SKCM) causes most skin cancer deaths.
- Limited effective therapeutic targets exist beyond BRAF V600F mutations.
Purpose of the Study:
- Identify novel therapeutic targets for SKCM.
- Provide genetic evidence for drug-targetable genes in SKCM treatment.
Main Methods:
- Utilized SMR analysis with cis-eQTL data for SKCM risk.
- Performed colocalization assays and HEIDI tests for causal inference.
- Constructed protein-protein interaction networks and conducted drug druggability predictions.
Main Results:
- Identified 13 genes associated with SKCM risk (5 protective, 8 harmful).
- SOX4 and MAFF demonstrated Class 1 causal evidence for SKCM.
- SOX4, MAFF, ACSF3, CDK10, SPG7, and TCF25 predicted as druggable targets.
Conclusions:
- The study provides genetic evidence supporting targeting specific genes for SKCM treatment.
- Identified druggable targets offer potential for novel therapeutic strategies in SKCM.
