Unveiling Common Transcriptomic Features between Melanoma Brain Metastases and Neurodegenerative Diseases

Area of Science:

• Oncology
• Neuroscience
• Genomics

Background:

• Melanoma brain metastases present significant clinical challenges due to poor outcomes.
• The molecular mechanisms enabling melanoma's adaptation to the brain microenvironment are not well understood.
• Emerging evidence suggests shared biological processes between melanoma brain metastases and neurodegenerative diseases.

Purpose of the Study:

• To investigate the transcriptional relationship between melanoma brain metastases and neurodegenerative diseases.
• To identify a potential neurodegenerative molecular signature in melanoma brain metastases.

Main Methods:

• In silico analysis comparing gene expression profiles.
• Transcriptional profiles of melanoma brain metastases, non-brain metastases, and non-tumor brain controls were analyzed.
• Functional enrichment analysis was performed on dysregulated genes.

Main Results:

• A distinct neurodegenerative signature was identified in melanoma brain metastases.
• Comparison with melanoma non-brain metastases revealed 53 dysregulated genes linked to extracellular matrix and development.
• Comparison with non-tumor brain controls identified 195 dysregulated genes involved in development, chromatin remodeling, and translation.
• ITGA10 and DNAJC6 were identified as key genes dysregulated in both melanoma brain metastases and neurodegenerative conditions.

Conclusions:

• Melanoma brain metastases exhibit a neurodegenerative molecular signature.
• The findings suggest shared pathways between melanoma brain metastasis and neurodegenerative diseases.
• ITGA10 and DNAJC6 are potential biomarkers for melanoma brain metastasis.
• An open-source web tool was developed for interactive exploration of the results.