Identification and targeting of centrosome amplification related signature genes for prognosis and therapy in skin cutaneous melanoma

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Background: Skin cutaneous melanoma (SKCM) is a highly aggressive cancer with significant mortality, necessitating novel prognostic markers and therapeutic strategies. Centrosome amplification (CA), a hallmark of genomic instability, contributes to cancer progression, but its role in SKCM remains unclear. Methods: Transcriptomic data from SKCM patients were analyzed to identify differentially expressed genes (DEGs) between SKCM and normal tissues. Centrosome amplification-related genes (CA-RGs) were selected based on centrosomal functions. Prognostic CA-RGs were identified using Cox regression and LASSO analyses, resulting in a CA-RG-based risk model. Single-cell RNA sequencing (scRNA-seq) was employed to investigate cellular mechanisms, and immune infiltration analyses were conducted to assess CA-RGs’ impacts on the tumor microenvironment. Results: Four CA-RGs (CDK2, KAT2B, NUBP1, CEP120) were identified as prognostic markers. A risk model effectively stratified patients by survival outcomes and was validated in external datasets. Immune infiltration analysis showed that low-risk patients had higher immune and stromal scores, with increased CD8+ T cells and M1 macrophages. ScRNA-seq analysis revealed interactions among fibroblasts, keratinocytes, and malignant cells, indicating CDK2 and KAT2B may promote tumor progression through intercellular signaling. Conclusions: This study identifies novel CA-RGs and establishes a robust risk model for SKCM prognosis. Insights into the immune microenvironment and intercellular interactions provide a foundation for targeted therapies, including immunotherapy, offering potential strategies for improving SKCM management.