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Updated: May 7, 2026
A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Identification of druggable targets in melanoma by multi-omics Mendelian randomization integrated with transcriptomic
Jiahua Xing1, Mingyong Yang1, Muzi Chen2
1Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Background:
Cutaneous melanoma (CM) is a highly lethal skin tumor. Some patients respond poorly to existing therapies, and developing new targeted therapies remains challenging.
Methods:
We combined the results of eQTLs, pQTLs, and genome-wide association study (GWAS) to identify potential causal effects of two target genes on CM, based on multi-omics Mendelian randomization (MR). Sensitivity analysis, co-localization analysis, and inverse MR analysis were also employed to verify the robustness of this causal relationship. Multi-omics data were then applied to explore the expression patterns of immune infiltration of the target genes and construct nomogram models.
Results:
The results showed that the gene prediction levels of EPS15L1 and HGS were associated with an increased risk of CM. Co-localization analysis revealed significant horizontal pleiotropy of the target gene, and reverse MR showed unidirectional causality of the targets. Multi-omics analysis comprehensively demonstrated the expression regulation pattern of the target genes in the CM immune-environment and identified interactions between EPS15L1 (Q9UBC2) and HGS (O14964) and doxorubicin, demonstrating the potential for drug application. The validity of the targets was further verified by molecular biology experiments.
Conclusion:
This study provides robust genetic and therapeutic evidence for targeting EPS15L1 and HGS in CM treatment.
Insights
This study identifies EPS15L1 and HGS as potential therapeutic targets for cutaneous melanoma (CM). Genetic analysis suggests these genes increase CM risk, offering new avenues for targeted treatment strategies.
Area of Science:
- Genetics
- Oncology
- Bioinformatics
Background:
- Cutaneous melanoma (CM) is a deadly skin cancer with limited treatment options for some patients.
- Developing novel targeted therapies for CM remains a significant challenge in oncology.
Purpose of the Study:
- To identify potential causal genes for cutaneous melanoma (CM) using multi-omics data.
- To investigate the therapeutic potential of identified genes in CM treatment.
Main Methods:
- Multi-omics Mendelian randomization (MR) integrating eQTLs, pQTLs, and GWAS.
- Sensitivity, co-localization, and inverse MR analyses to confirm causality.
- Exploration of gene expression patterns in the CM immune microenvironment and nomogram construction.
Main Results:
- EPS15L1 and HGS gene expression levels were associated with increased CM risk.
- Co-localization and reverse MR analyses confirmed a unidirectional causal relationship.
- Multi-omics analysis revealed gene interactions with doxorubicin, suggesting therapeutic potential, further validated by experiments.
Conclusions:
- Provides robust genetic evidence supporting EPS15L1 and HGS as therapeutic targets for CM.
- Highlights the potential of targeting EPS15L1 and HGS for novel CM treatment strategies.
