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Background <p>Lack of reliable biomarkers for early detection and monitoring contributes to the poor prognosis of pancreatic ductal adenocarcinoma (PDAC), as the current clinical marker, CA19-9, lacks adequate specificity and sensitivity.</p> Methods <p>Serum concentrations of ALPPL2-positive and THBS2-positive exosomes were measured using an ExoView assay in two cohorts: a cohort of 219 subjects, including non-disease controls and patients with early- or late-stage PDAC, and a longitudinal cohort of 26 patients with advanced PDAC undergoing treatment.</p> Results <p>Exosomal ALPPL2 and THBS2 distinguished non-cancer cases from PDAC with high accuracy; area under the curve (AUC) values = 0.983, 0.993, and 0.983 for ALPPL2, THBS2, and the dual marker combination, respectively. Additionally, changes in the concentrations of ALPPL2<sup>+</sup> and THBS2<sup>+</sup> exosomes strongly correlated with radiographic tumor size changes during treatment in both CA19-9-elevated (<i>p</i> = 0.016 and 0.014 for ALPPL2 and THBS2, respectively) and non-elevated patients (<i>p</i> = 0.003 and 0.006 for ALPPL2 and THBS2, respectively).</p> Conclusions <p>Serum exosomal ALPPL2 and THBS2 can accurately discriminate patients with PDAC from individuals with non-cancerous conditions and healthy controls. Changes in serum exosomal ALPPL2 and THBS2 levels significantly correlate with patients’ response to treatment in both CA19-9-elevated and non-elevated patients.</p>

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Exosomal ALPPL2 and THBS2 as biomarkers for early detection and disease monitoring of pancreatic ductal adenocarcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月3日

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  • Kuntal Halder,
  • Erkut H. Borazanci,
  • Gayle S. Jameson,
  • Wei Lin,
  • Amber Vrana,
  • Derek Cridebring,
  • Susan Tsai,
  • Mohammed Aldakkak,
  • Douglas B. Evans,
  • Masamichi Hayashi,
  • Haruyoshi Tanaka,
  • Mitsuro Kanda,
  • Ajay Goel,
  • Daniel D. Von Hoff,
  • Haiyong Han

摘要

Background

Lack of reliable biomarkers for early detection and monitoring contributes to the poor prognosis of pancreatic ductal adenocarcinoma (PDAC), as the current clinical marker, CA19-9, lacks adequate specificity and sensitivity.

Methods

Serum concentrations of ALPPL2-positive and THBS2-positive exosomes were measured using an ExoView assay in two cohorts: a cohort of 219 subjects, including non-disease controls and patients with early- or late-stage PDAC, and a longitudinal cohort of 26 patients with advanced PDAC undergoing treatment.

Results

Exosomal ALPPL2 and THBS2 distinguished non-cancer cases from PDAC with high accuracy; area under the curve (AUC) values = 0.983, 0.993, and 0.983 for ALPPL2, THBS2, and the dual marker combination, respectively. Additionally, changes in the concentrations of ALPPL2+ and THBS2+ exosomes strongly correlated with radiographic tumor size changes during treatment in both CA19-9-elevated (p = 0.016 and 0.014 for ALPPL2 and THBS2, respectively) and non-elevated patients (p = 0.003 and 0.006 for ALPPL2 and THBS2, respectively).

Conclusions

Serum exosomal ALPPL2 and THBS2 can accurately discriminate patients with PDAC from individuals with non-cancerous conditions and healthy controls. Changes in serum exosomal ALPPL2 and THBS2 levels significantly correlate with patients’ response to treatment in both CA19-9-elevated and non-elevated patients.