Pan-Cancer Analysis and Validation of NT5DC2: Emphasizing Its Prognostic Significance and Immunological Role in TNBC

Background 5′-Nucleotidase Domain Containing 2 (NT5DC2), a cNT5-II family member catalyzing nucleotide hydrolysis, plays a crucial role in tumor initiation and progression. This study aims to elucidate NT5DC2’s potential role in multiple cancers and confirm its oncogenic significance in triple-negative breast cancer (TNBC). Methods Multiple databases analyzed NT5DC2 expression patterns and assessed its diagnostic and prognostic value in cancers. Immune correlation analyses were conducted using ESTIMATE and CIBERSORT. KEGG pathway enrichment analysis explored NT5DC2-associated molecular pathways. To further investigate its role in TNBC, comprehensive bioinformatics analyses, including gene expression profiling, single-cell RNA sequencing analysis, immune infiltration assessment, and gene set enrichment analysis (GSEA). Finally, in vitro experiments were conducted to validate NT5DC2’s oncogenic role in TNBC. Results Our findings indicate that high NT5DC2 expression is associated with poor prognosis and holds significant clinical diagnostic value across multiple cancer types. NT5DC2 is highly expressed in TNBC and correlates with unfavorable outcomes. Single-cell RNA sequencing analysis reveals that NT5DC2 is predominantly expressed in epithelial cells, where it regulates immune cells through the MIF signaling pathway. Enrichment and immune infiltration analyses indicate that NT5DC2 is closely linked to an immunosuppressive tumor microenvironment. In vitro experiments demonstrate that NT5DC2 knockdown significantly inhibits TNBC cell growth, underscoring its potential as a therapeutic target. Conclusion Our study demonstrates that NT5DC2 functions as an oncogene in multiple cancer types. It holds considerable clinical diagnostic significance and is intricately linked to an immunosuppressive tumor microenvironment, particularly in TNBC.