Abstract
BACKGROUND: Skin cutaneous melanoma (SKCM) is a highly invasive malignant tumor with poor prognosis in the advanced stage and prominent problems of immunotherapy resistance. Heat shock protein A8 (HSPA8) is involved in tumor progression and immune escape in various cancers, but its role in SKCM remains unclear. This study aimed to explore the role of HSPA8 in SKCM. METHODS: Based on the SKCM transcriptome, clinical data, and related biological information from public databases including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Human Protein Atlas (HPA), and cGSCALite platform, we used differential analysis, survival analysis, receiver operating characteristic curve (ROC), Cox regression, functional enrichment analysis, immunological correlation analysis, and molecular docking to systematically evaluate the biological role of HSPA8 in SKCM. RESULTS: HSPA8 was highly expressed in SKCM tissues compared with normal tissues, and exhibited significant diagnostic efficacy for SKCM. Multivariate Cox regression analysis confirmed that HSPA8 was an independent risk factor closely related to the poor prognosis of SKCM patients. Functional enrichment analysis showed that HSPA8-related genes were mainly enriched in tumor-related pathways such as cytokine-cytokine receptor interaction and TGF-β signaling pathway. Immunological correlation analysis revealed that HSPA8 was closely associated with the construction of an immunosuppressive microenvironment in SKCM. In addition, drug sensitivity analysis and molecular docking showed potential sensitivity to GSK-J4 and Nutlin-3a(-) based on in silico prediction. CONCLUSION: HSPA8 is a biomarker related to the prognosis and immunity of SKCM, which may promote tumor progression by regulating the immunosuppressive microenvironment. This study clarifies the biological role of HSPA8 in SKCM and provides a new target and theoretical basis for the precision diagnosis and immunotherapy of SKCM.