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Related Experiment Video

Updated: May 14, 2026

An Orthotopic Resectional Mouse Model of Pancreatic Cancer
07:17

An Orthotopic Resectional Mouse Model of Pancreatic Cancer

Published on: September 24, 2020

Biological Borderline Resectable Pancreatic Cancer Represents a Genetically and Immunologically Aggressive Subtype: A

Yu Arai1, Atsuhiro Masuda1, Masahiro Tsujimae1

  • 1Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

Annals of Surgery
|May 13, 2026
PubMed

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Summary

High CA19-9 levels in pancreatic cancer indicate a biologically aggressive subtype with worse survival and increased genomic alterations. This finding suggests a need for intensified treatment strategies even for resectable tumors.

Area of Science:

  • Oncology
  • Genomics
  • Immunology

Background:

  • Biological borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) is defined by high CA19-9 levels (≥500 U/mL) and is linked to poor prognosis.
  • The molecular and immunopathological characteristics of this PDAC subtype are not fully understood.

Purpose of the Study:

  • To investigate the molecular and immunopathological features of PDAC with high preoperative CA19-9 levels.
  • To correlate these features with clinical outcomes, including cancer-specific survival (CSS) and recurrence patterns.

Main Methods:

  • Retrospective analysis of 144 patients with PDAC who underwent upfront surgical resection.
  • Stratification into three groups based on preoperative CA19-9 levels: <37 U/mL, 37-499 U/mL, and ≥500 U/mL (biological BR).
Keywords:
Biological Borderline Resectable Pancreatic CancerPrognosisdriver gene alterationsimmunosuppressive microenvironment

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  • Evaluation of clinicopathological data, CSS, driver gene alterations (KRAS, TP53, CDKN2A, SMAD4), and immune microenvironment (tumor-infiltrating lymphocytes, tertiary lymphoid structures).

    • Main Results:

    • Patients with CA19-9 ≥500 U/mL had significantly worse CSS.
    • A stepwise increase in mutational burden and CDKN2A/p16 alterations was observed with rising CA19-9 levels.
    • Tertiary lymphoid structure (TLS) positivity and CD8+ T-cell density decreased with increasing CA19-9, alongside a stepwise increase in peritoneal recurrence.

    Conclusions:

    • Elevated preoperative CA19-9 (≥500 U/mL) identifies a biologically aggressive PDAC subset characterized by increased genomic alterations and an immunosuppressive microenvironment.
    • This high-risk marker warrants consideration for intensified perioperative strategies, even in radiographically resectable cases.
    • Understanding these features can guide personalized treatment approaches for PDAC.