Work

The role of CD26 in breast cancer and its pan-cancer analysis

Year: 2026

Type: article

Abstract: BACKGROUND: CD26 (DPP4) is shown in literature to be implicated in multiple tumors and antitumor immunity, yet its pan-cancer and context-dependent roles remain imprecisely defined. This study comprehensively characterizes the clinical relevance of CD26 and its association with invasion-related features and immunotherapy-relevant immune infiltration and response-associated biomarkers, and to validate key findings in breast cancer cells. METHODS: The integrated pan-cancer analysis of CD26 was performed using public databases, assessing its expression patterns, associations with cancer staging and prognostic value. Co-expression and protein-interaction data were used for GO/KEGG enrichment to infer potential biological pathways. Correlations between CD26 and immune cell infiltration, cancer-associated fibroblasts (CAFs), immune checkpoints, tumor mutational burden (TMB), microsatellite instability (MSI), and neoantigen load were systematically evaluated. R software and online bioinformatics tools were employed. Additionally, qPCR, western blot and other in-vitro experiments compared CD26 expression in MCF-7 breast cancer cells and MCF-10A normal breast epithelial cells, and examined the effects of pharmacologic CD26 inhibition (alogliptin) on proliferation, invasion, and MMP9 expression in vitro. RESULTS: CD26 exhibited broad but low tissue specificity and was significantly upregulated in multiple malignancies compared with normal tissues, particularly in highly aggressive tumors (P < 0.01). Higher CD26 expression was associated with advanced pathological stage and adverse prognosis in several tumor types (p < 0.01), including breast cancer, while exhibiting a favorable prognostic association in a subset of tumors, indicating context-dependent relationships. Functional enrichment suggested involvement of CD26-related networks in chemokine signaling and EMT-related processes. CD26 expression correlated with estimated immune infiltration in 34 of 38 tumor types, including CD4+ and CD8+ T cells and CAFs, and was associated with multiple immune checkpoints, as well as TMB, MSI and neoantigens in selected cancers. In vitro, CD26 was elevated in MCF-7 versus MCF-10A cells (p < 0.05), and alogliptin treatment reduced MCF-7 cell proliferation and invasion (p < 0.05), accompanied by decreased MMP9 expression (p < 0.05). CONCLUSIONS: This study presents an integrative pan-cancer framework linking CD26 expression to immune infiltration, together with in vitro observations in breast cancer cells, offering a comprehensive pan-cancer and experimental characterization of CD26. CD26 might be a novel prognostic biomarker candidate and therapeutic target to counteract tumor development in highly aggressive cancer.

Source: BMC Cancer

DOI: 10.1186/s12885-026-15656-5