Pan-cancer analysis and validation of NT5DC2: emphasizing its prognostic significance and immunological role in TNBC

5'-Nucleotidase Domain Containing 2 (NT5DC2), a member of the cNT5-II family that catalyzes nucleotide hydrolysis, plays a critical role in tumor initiation and progression. This study aims to elucidate the role of NT5DC2 across multiple cancers and to confirm its oncogenic significance in triple-negative breast cancer (TNBC).

NT5DC2 expression patterns were analyzed across multiple databases to evaluate its diagnostic and prognostic value in various cancers. Immune correlation analyses were performed using ESTIMATE and CIBERSORT algorithms. KEGG pathway enrichment analysis was used to explore NT5DC2-associated molecular pathways. In TNBC, comprehensive bioinformatics approaches, including gene expression profiling, single-cell RNA sequencing, immune infiltration analysis, and gene set enrichment analysis (GSEA), were employed. Additionally, in vitro experiments were conducted to validate the oncogenic role of NT5DC2 in TNBC.

High NT5DC2 expression was associated with poor prognosis and demonstrated significant clinical diagnostic value across several cancer types. In TNBC, NT5DC2 was found to be highly expressed and correlated with adverse outcomes. Single-cell RNA sequencing revealed that NT5DC2 is predominantly expressed in epithelial cells and may regulate immune cell behavior through the MIF signaling pathway. Enrichment and immune infiltration analyses further indicated that NT5DC2 is strongly associated with an immunosuppressive tumor microenvironment (TME). In vitro experiments showed that NT5DC2 knockdown significantly suppressed TNBC cell growth, whereas its overexpression exerted opposing effects, highlighting its therapeutic potential.

This study identifies NT5DC2 as an oncogene with broad clinical relevance across multiple cancers. In TNBC, NT5DC2 contributes to an immunosuppressive microenvironment and represents a promising diagnostic marker and therapeutic target.