Association of stromal type IV collagen and prognosis in neoadjuvant chemotherapy-treated pancreatic cancer.

cancer-associated fibroblasts neoadjuvant chemotherapy pancreatic ductal adenocarcinoma stroma type IV collagen

Journal

Japanese journal of clinical oncology
ISSN: 1465-3621
Titre abrégé: Jpn J Clin Oncol
Pays: England
ID NLM: 0313225

Informations de publication

Date de publication:
24 Aug 2024
Historique:
received: 31 05 2024
accepted: 09 08 2024
medline: 24 8 2024
pubmed: 24 8 2024
entrez: 24 8 2024
Statut: aheadofprint

Résumé

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis due to its low surgical eligibility and resistance to chemotherapy. Abundant stroma is characteristic of PDAC, and cancer-associated fibroblasts (CAFs) are a major stromal constituent, contributing to chemoresistance. Because neoadjuvant chemotherapy (NAC) is included in PDAC treatment as a standard regimen, the role of CAFs in NAC resistance must be studied. Although type IV collagen (COLIV) is present in the tumor of PDAC, the association between COLIV and disease advancement of NAC-treated PDAC is unclear. Using a cohort of NAC-treated patients with PDAC, we examined clinicopathological data and conducted immunohistochemical analysis of COLIV in tissue specimens prepared from surgically resected pancreas. Our analysis revealed that ~50% of the cases were positive for COLIV in the stroma and diffuse COLIV staining was an independent poor prognosis factor alongside high serum CA19-9 before NAC treatment (>37 U/mL) and postsurgical residual tumors. Based on these findings, we propose that stromal COLIV staining can be used to predict prognosis in NAC-treated patients with PDAC after surgery. Additionally, these findings suggest a possibility that stromal COLIV staining indicates resistance to anticancer drugs and/or contributes to malignancy in PDAC.

Sections du résumé

BACKGROUND BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis due to its low surgical eligibility and resistance to chemotherapy. Abundant stroma is characteristic of PDAC, and cancer-associated fibroblasts (CAFs) are a major stromal constituent, contributing to chemoresistance. Because neoadjuvant chemotherapy (NAC) is included in PDAC treatment as a standard regimen, the role of CAFs in NAC resistance must be studied. Although type IV collagen (COLIV) is present in the tumor of PDAC, the association between COLIV and disease advancement of NAC-treated PDAC is unclear.
METHODS METHODS
Using a cohort of NAC-treated patients with PDAC, we examined clinicopathological data and conducted immunohistochemical analysis of COLIV in tissue specimens prepared from surgically resected pancreas.
RESULTS AND CONCLUSIONS CONCLUSIONS
Our analysis revealed that ~50% of the cases were positive for COLIV in the stroma and diffuse COLIV staining was an independent poor prognosis factor alongside high serum CA19-9 before NAC treatment (>37 U/mL) and postsurgical residual tumors. Based on these findings, we propose that stromal COLIV staining can be used to predict prognosis in NAC-treated patients with PDAC after surgery. Additionally, these findings suggest a possibility that stromal COLIV staining indicates resistance to anticancer drugs and/or contributes to malignancy in PDAC.

Identifiants

pubmed: 39180719
pii: 7740617
doi: 10.1093/jjco/hyae118
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Renee Medical Corporation
Organisme : Okinaka Memorial Institute for Medical Research
Organisme : Juntendo University School of Medicine Project grant
Organisme : Japan Society for the Promotion of Science
ID : 21 K07127

Informations de copyright

© The Author(s) 2024. Published by Oxford University Press.

Auteurs

Yasuhiro Nakamura (Y)

Department of Orthopaedics, Faculty of Medicine, Juntendo University, Tokyo, Japan.
Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Department of Molecular Pathogenesis, Juntendo University Graduate School of Medicine, Tokyo, Japan.

Takehiro Yasukawa (T)

Department of Molecular Pathogenesis, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Department of Pathology and Oncology, Juntendo University Faculty of Medicine, Tokyo, Japan.

Yuki Fukumura (Y)

Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan.

Yoshinori Takeda (Y)

Department of Hepatobiliary and Pancreatic Surgery, Juntendo University School of Medicine, Tokyo Japan.

Hiroshi Imamura (H)

Department of Hepatobiliary and Pancreatic Surgery, Juntendo University School of Medicine, Tokyo Japan.

Yang Shi (Y)

Department of Molecular Pathogenesis, Juntendo University Graduate School of Medicine, Tokyo, Japan.

Mu Li (M)

Department of Molecular Pathogenesis, Juntendo University Graduate School of Medicine, Tokyo, Japan.

Masaaki Abe (M)

Department of Pathology and Oncology, Juntendo University Faculty of Medicine, Tokyo, Japan.

Saya Uyama (S)

Department of Pathology and Oncology, Juntendo University Faculty of Medicine, Tokyo, Japan.

Kazunori Kajino (K)

Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan.

Muneaki Ishijima (M)

Department of Orthopaedics, Faculty of Medicine, Juntendo University, Tokyo, Japan.
Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, Tokyo, Japan.

Akio Saiura (A)

Department of Hepatobiliary and Pancreatic Surgery, Juntendo University School of Medicine, Tokyo Japan.

Akira Orimo (A)

Department of Molecular Pathogenesis, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Department of Pathology and Oncology, Juntendo University Faculty of Medicine, Tokyo, Japan.

Classifications MeSH