Exploring the Underlying Molecular Connections: A Bioinformatics Approach to Link Melanoma and Parkinson's Disease

Bo Yuan ^1,2* Limei Zhang ³ Xu Zheng ⁴ Moli Wu ⁴ Qijun Yao ² Haoran Chen ² Zhiqiang Ye ²

• ¹ Second Affiliated Hospital of Dalian Medical University, Dalian, China
• ² Department of Reparative and Reconstructive Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China
• ³ Department of Radiology, Dalian Municipal Central Hospital, Dalian, Liaoning Province, China
• ⁴ College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning Province, China

Melanoma, an aggressive skin cancer, and Parkinson's disease (PD), a progressive neurodegenerative disorder, exhibit a positive epidemiological association, the molecular basis of which remains elusive. This link has been consistently observed across diverse populations, hinting at overlapping pathogenic mechanisms. To unravel this, we conducted a comprehensive analysis of gene expression profiles in PD and melanoma, aiming to identify common differentially expressed genes (DEGs) that may underlie this association. Analyzing two independent public genomic datasets, we pinpointed 41 overlapping DEGs related to both PD and melanoma. Notably, VSNL1, ATP6V1G2, and DNM1 were significantly down-regulated in patients with both conditions. VSNL1, linked to synaptic vesicle fusion, may affect neuronal communication impaired in PD. ATP6V1G2, a V-ATPase subunit, could contribute to melanoma's pH dysregulation. DNM1, crucial for vesicle trafficking, might impact cellular transport anomalies in both diseases. To probe the regulation of these DEGs, we constructed networks involving transcription factors (TFs), DEGs, and microRNAs (miRNAs), and established protein-protein interaction (PPI) networks to identify hub genes central to disease pathology. We also explored the interplay between PD, melanoma, and immune cell infiltration, seeking correlations between hub gene expression and specific immune cell subsets, offering insights into disease immunology. Molecular docking studies identified retinoic acid as a potential therapeutic agent targeting VSNL1, ATP6V1G2, and DNM1, presenting a novel treatment approach. Our study not only uncovers potential biomarkers for early diagnosis and prognosis but also reveals new therapeutic targets. The discovery of retinoic acid as a promising agent signifies a major advancement in drug development for these diseases. By elucidating shared molecular pathways, our comprehensive analysis deepens the understanding of the molecular interplay between PD and melanoma, paving the way for future research and personalized treatment strategies.