Re-Analysis of GSE88741 Human Melanocytes Versus SK-Mel-28 Melanoma Cell Line

Abstract

The original study investigated the extreme genomic instability of melanoma, focusing on how mutations and dysregulation of RNAbinding proteins, particularly CELF1, contribute to tumor progression and poor patient outcomes. We reanalyzed the GEO dataset GSE88741 to refine the molecular portrait of melanoma and identify actionable vulnerabilities. The workflow first retrieved raw counts and metadata from ARCHS4, assembled them into an AnnData object, and performed differential expression analysis with limmavoom to generate a gene signature. This signature was then subjected to enrichment analysis using Enrichr across GO, KEGG, ChEA and KOMP2 libraries, and interrogated in PerturbSeqr to find smallmolecule and gene perturbations that recapitulate or counter the observed expression changes. The reanalysis revealed a pronounced upregulation of ribosomal biogenesis, protein trafficking, and MYCdriven transcriptional programs, consistent with a rapidly proliferating, dedifferentiated melanoma state, while genes involved in immune signaling and neuronal architecture were markedly downregulated. PerturbSeqr highlighted proteasome/ubiquitin inhibitors and MAPK pathway modulators as strong mimickers or reversers, underscoring these pathways as potential therapeutic targets to counteract the malignant phenotype.