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Background <p>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.</p> Methods <p>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.</p> Results <p>CD26 exhibited broad but low tissue specificity and was significantly upregulated in multiple malignancies compared with normal tissues, particularly in highly aggressive tumors (<i>P</i> &lt; 0.01). Higher CD26 expression was associated with advanced pathological stage and adverse prognosis in several tumor types (<i>p</i> &lt; 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<sup>+</sup> and CD8<sup>+</sup> 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 (<i>p</i> &lt; 0.05), and alogliptin treatment reduced MCF-7 cell proliferation and invasion (<i>p</i> &lt; 0.05), accompanied by decreased MMP9 expression (<i>p</i> &lt; 0.05).</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月30日

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  • Runyi Tao,
  • Bohao Liu,
  • Shan Gao,
  • Jingyi Zhang,
  • Jizhao Wang,
  • Qiuyu Gong,
  • Xingzhuo Zhu,
  • Yilong Zhao,
  • Jiaqi Huang,
  • Chenrong Zhang,
  • Yixing Li,
  • Zhiyu Wang,
  • Guangjian Zhang

摘要

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.