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Background <p>CD44v6-positive extracellular vesicles (EVs) released by cancer cells drive tumor progression and liver metastasis. This study aimed to evaluate CD44v6-positive extracellular vesicles (EVs) as prognostic markers for pancreatic ductal adenocarcinoma (PDAC), a disease with poor prognosis.</p> Methods <p>Plasma samples from 100 patients with hepatobiliary and pancreatic diseases were retrospectively analyzed. Non-pancreatic and unresectable pancreatic cancer cases were included as control groups for cross-sectional comparisons, whereas prognostic analysis using preoperative plasma samples was limited to resected PDAC. EVs were defined based on CD9, CD63, and CD81 membrane antigens, and the proportion of CD44v6-positive EVs was measured using nano-flow cytometry. CD44v6 expression in resected PDAC tissues was assessed using immunohistochemistry.</p> Results <p>The proportion of CD44v6-positive EVs was significantly higher in patients with pancreatic cancer than in those without cancer (<i>P</i> = 0.0009). High CD44v6 expression in resected PDAC tissues correlated with elevated CD44v6-positive EVs in the plasma. Patients with CD44v6-positive EVs ≥ 31% had significantly poorer recurrence-free survival (<i>P</i> = 0.0008) and overall survival (<i>P</i> = 0.045) than those with &lt; 31% EVs. Multivariate analysis confirmed CD44v6-positive EVs ≥ 31% were independent prognostic factors for recurrence-free (<i>P</i> = 0.005) and overall survival (<i>P</i> = 0.037), and a predictor of early liver metastasis (<i>P</i> = 0.001).</p> Conclusions <p>These findings highlight the potential of preoperative quantification of CD44v6-positive EVs as a biomarker for risk stratification and treatment optimization in PDAC.</p>

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Preoperative CD44v6-positive extracellular vesicles as a prognostic biomarker in pancreatic ductal adenocarcinoma

  • 期刊论文

  • 发表日期：

    2026年1月11日

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  • Yosuke Uematsu,
  • Sachiko Matsuda,
  • Minoru Kitago,
  • Sho Uemura,
  • Gaku Shimane,
  • Yutaka Nakano,
  • Masayuki Tanaka,
  • Shutaro Hori,
  • Yasushi Hasegawa,
  • Yuta Abe,
  • Yohei Masugi,
  • Ryo Takemura,
  • Yuko Kitagawa

摘要

Background

CD44v6-positive extracellular vesicles (EVs) released by cancer cells drive tumor progression and liver metastasis. This study aimed to evaluate CD44v6-positive extracellular vesicles (EVs) as prognostic markers for pancreatic ductal adenocarcinoma (PDAC), a disease with poor prognosis.

Methods

Plasma samples from 100 patients with hepatobiliary and pancreatic diseases were retrospectively analyzed. Non-pancreatic and unresectable pancreatic cancer cases were included as control groups for cross-sectional comparisons, whereas prognostic analysis using preoperative plasma samples was limited to resected PDAC. EVs were defined based on CD9, CD63, and CD81 membrane antigens, and the proportion of CD44v6-positive EVs was measured using nano-flow cytometry. CD44v6 expression in resected PDAC tissues was assessed using immunohistochemistry.

Results

The proportion of CD44v6-positive EVs was significantly higher in patients with pancreatic cancer than in those without cancer (P = 0.0009). High CD44v6 expression in resected PDAC tissues correlated with elevated CD44v6-positive EVs in the plasma. Patients with CD44v6-positive EVs ≥ 31% had significantly poorer recurrence-free survival (P = 0.0008) and overall survival (P = 0.045) than those with < 31% EVs. Multivariate analysis confirmed CD44v6-positive EVs ≥ 31% were independent prognostic factors for recurrence-free (P = 0.005) and overall survival (P = 0.037), and a predictor of early liver metastasis (P = 0.001).

Conclusions

These findings highlight the potential of preoperative quantification of CD44v6-positive EVs as a biomarker for risk stratification and treatment optimization in PDAC.