{
  "abstract": "Triple-negative breast cancer (TNBC) lacks reliable biomarkers for early detection and remains a highly aggressive disease. Ephrin type-A receptor 2 (EphA2), a receptor tyrosine kinase frequently overexpressed in advanced cancers, undergoes MMP14-mediated cleavage that releases soluble N-terminal fragments. Here, we investigated the diagnostic and functional significance of this fragment in TNBC. Immunohistochemical analysis of clinical specimens revealed elevated EphA2 expression in TNBC tissues, with a trend toward higher levels in tumors of advanced stage and grade. To enable non-invasive detection, we established a dual-epitope sandwich ELISA targeting spatially distinct regions of the EphA2 extracellular domain. The assay showed concentration-dependent detection of recombinant EphA2 (EC₅₀, 48 ng/mL) and detected soluble EphA2 in TNBC cell-conditioned media. Serum analysis showed significantly higher EphA2 levels in TNBC patients compared with healthy controls (median 93.3 vs 25.6 ng/mL). In this exploratory cohort, ROC analysis yielded an AUC of 0.912 (95% CI, 0.862-0.962), with a sensitivity of 95.0% (95% CI, 86.3-98.6%) and a specificity of 78.3% (95% CI, 66.4-86.9%), and higher levels were associated with lymph node metastasis and higher histological grade. Functionally, recombinant EphA2-P328 promoted TNBC-cell migration and induced cell context-dependent changes in EMT-associated markers in vitro. Collectively, these findings support the soluble N-terminal EphA2 fragment as a candidate serum biomarker and an in vitro modulator of TNBC cell migration, warranting validation in larger independent cohorts and further mechanistic investigation.",
  "abstract_shown": true,
  "affiliations": [
    "Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.",
    "School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan.",
    "Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; Division of Urology, Department of Surgery, Far Eastern Memorial Hospital, New Taipei City, Taiwan.",
    "Taiwan Autoantibody Biobank Initiative, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.",
    "Ph.D. Program in Innovative Medical Technology Research and Development Industry, Taipei Medical University, Taipei, Taiwan.",
    "Department of Laboratory Medicine, Lotung PohAi Hospital, Lo-Hsu Medical Foundation, Yilan, Taiwan; Ph.D. Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.",
    "Ph.D. Program in Innovative Medical Technology Research and Development Industry, Taipei Medical University, Taipei, Taiwan; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan.",
    "Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.",
    "Department of Laboratory Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Tsai-Yu Lin"
    },
    {
      "affs": [
        1
      ],
      "name": "Fu-Ling Chang",
      "orcid": "0000-0001-6711-5820"
    },
    {
      "affs": [
        2
      ],
      "name": "Shang-Ju Hsieh"
    },
    {
      "affs": [
        3
      ],
      "name": "Jia-Huei Zheng"
    },
    {
      "affs": [
        4
      ],
      "name": "Yen-Chen Lu"
    },
    {
      "affs": [
        5
      ],
      "name": "Ming-Hui Cheng",
      "orcid": "0000-0002-4221-6809"
    },
    {
      "affs": [
        6
      ],
      "name": "Keng-Chang Tsai"
    },
    {
      "affs": [
        7
      ],
      "name": "Wei-Chun HuangFu"
    },
    {
      "affs": [
        8
      ],
      "name": "Ching-Sheng Hung"
    },
    {
      "name": "Yu-Ching Lee"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/en3v17cktv3xa.bib",
  "cited_by": 0,
  "doi": "10.1016/j.tranon.2026.103074",
  "fulltext_url": "https://europepmc.org/articles/PMC13685997",
  "id": "en3v17cktv3xa",
  "issns": [
    "1936-5233"
  ],
  "landing_url": "https://europepmc.org/article/MED/42868712",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2804|Axon Guidance and Neuronal Signaling"
    ]
  ],
  "openalex": "W7221713865",
  "pdf_url": "https://europepmc.org/articles/PMC13685997?pdf=render",
  "pmcid": "PMC13685997",
  "pmid": "42868712",
  "published": "2026-10-13",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/en3v17cktv3xa.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:00Z",
      "native_id": "MED:42868712",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42868712"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2804|Axon Guidance and Neuronal Signaling",
      "subfield": "neuroscience"
    }
  ],
  "title": "Soluble N-terminal EphA2 fragment as a diagnostic biomarker and functional mediator of tumor progression in triple-negative breast cancer.",
  "title_text": "Soluble N-terminal EphA2 fragment as a diagnostic biomarker and functional mediator of tumor progression in triple-negative breast cancer.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:00Z",
  "url": "https://research.draconitic.com/paper/en3v17cktv3xa",
  "venue": "Translational oncology",
  "versions": []
}