Pan-Cancer Analysis of the Immunomodulatory Roles and Prognostic Value of PDXP and Experimental Verification in SKCM

Multiple public databases, including TCGA, GEO, and TARGET, were utilized to comprehensively analyze pyridoxal phosphatase (PDXP) expression profiles across 34 cancer types. We further explored the associations of PDXP expression with clinicopathological features, tumor immune microenvironment, genomic heterogeneity, functional signaling pathways, and therapeutic response. In addition, in vitro and in vivo experiments were performed to preliminarily validate the potential mechanism linking PDXP expression to melanoma progression. PDXP exhibited aberrant differential expression in most cancer types and tended to be highly expressed in malignant tumor cells. PDXP expression was correlated with overall survival outcomes in 14 cancer types. In most investigated tumors, PDXP expression was significantly associated with the expression of immunoregulatory and immune checkpoint genes, as well as the general landscape of the tumor immune microenvironment. Correlation analysis of genomic characteristics indicated that PDXP may serve as a potential immune-related biomarker in skin cutaneous melanoma (SKCM). Functional enrichment and signaling pathway analysis showed that elevated PDXP expression in SKCM was correlated with enhanced tumor cell proliferative activity. In vitro and in vivo functional experiments demonstrated that PDXP knockdown significantly suppressed colony formation and migration of melanoma cells, induced G2/M phase cell cycle arrest, and increased cell apoptosis. These findings suggest that PDXP is associated with malignant phenotypes of melanoma cells, which are accompanied by changes in protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling activity. Moreover, we established a prognostic model with moderate predictive performance for melanoma using least absolute shrinkage and selection operator (LASSO)-Cox regression, providing a preliminary prognostic reference for SKCM patients.