Abstract 65P
Background
Malignant melanoma (MM) poses a significant clinical challenge necessitating improved diagnostic markers and therapeutic targets. Desmocollin-3 (DSC3), part of the desmosomal cadherin family, plays a role in epithelial-mesenchymal transition (EMT)-driven tumorigenesis. This study explores DSC3's functional and clinical significance as a diagnostic marker and therapeutic target in MM.
Methods
In a study 35 participants were divided into control, primary melanoma, and advanced MM groups. Tissue samples were collected for RNA isolation and qRT-PCR to measure DSC3 expression. Immunohistochemistry staining assessed DSC3 levels. Melanoma cell lines were transduced with DSC3-targeting shRNA, validated via qRT-PCR and Western blotting. Invasion, migration, cell cycle, and real-time cell analysis were performed. Protein levels were examined via Western blotting. Whole Genome Sequencing (WGS) identified genomic alterations. In silico mutation analysis evaluated DSC3 mutations.
Results
Our investigation consistently demonstrates the downregulation of DSC3 during melanomagenesis, affecting both melanoma cell lines and an independent tissue cohort. Furthermore, reduced levels of DSC3 are strongly linked with unfavorable clinical outcomes and are significantly correlated with disease severity and key metastatic biomarkers, including BRAF and NRAS mutations. Functional experiments provide compelling evidence that a decrease in DSC3 expression enhances cell scattering, invasion, and migration, thereby facilitating EMT-driven tumor progression and metastasis. Remarkably, whole-exome sequencing uncovers novel somatic loss-of-function mutations in DSC3, offering valuable insights into potential genetic drivers of melanoma pathogenesis.
Conclusions
Our study not only provides crucial insights into the role of DSC3 in melanoma but also underscores its relevance within the context of unraveling the mysteries of glycans in humans and pathogens. This comprehensive understanding sets the stage for the development of targeted therapies with a specific emphasis on glycoproteins and glycosylation, promising improved outcomes for MM patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.