Comprehensive analysis reveals MCM4 as a biomarker for guiding therapies and immunomodulatory role in skin cutaneous melanoma.

: Skin cutaneous melanoma (SKCM) is a malignant tumor characterized by aggressive invasion and a high tendency for metastasis. This study explores the potential of MCM4 as a biomarker for SKCM and its impact on the tumor microenvironment (TME). : A comprehensive analysis of MCM4 was conducted using public databases to characterize the expression, genomic alterations, and clinical significance of MCM4 in pan-cancer, including SKCM. Bioinformatics tools were employed to identify upstream regulators of MCM4. The functional mechanisms of MCM4 in SKCM were explored through correlation, differential, and enrichment analyses. Immune infiltration and drug sensitivity were assessed to understand the role of MCM4 in the TME and its potential therapeutic implications. Functional experiments were performed in A375 and SK-MEL-28 cells. : MCM4 were significantly upregulated in tumors. Survival curves indicated that patients with high MCM4 expression had poor survival advantage. SRF was identified as a potential transcription factor regulating MCM4. Functional enrichment revealed a positive correlation between MCM4 and cell cycle-related pathways, and a negative correlation with immune effector process-related pathways. High MCM4 expression was associated with "cold" tumor characteristics. Immunotherapy response analysis demonstrated higher response rates in patients with low MCM4 expression. Drug sensitivity analysis suggested potential therapeutic drug options based on MCM4 expression. Functional experiments confirmed the oncogenesis effects of MCM4 in SKCM cells. : MCM4 is a potential prognostic biomarker and predictor of immunotherapy response in SKCM patients.