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

Author:

Nakamura Yasuhiro1234,Yasukawa Takehiro45ORCID,Fukumura Yuki6,Takeda Yoshinori7ORCID,Imamura Hiroshi7,Shi Yang4,Li Mu4,Abe Masaaki5,Uyama Saya5,Kajino Kazunori6,Ishijima Muneaki123,Saiura Akio7,Orimo Akira45

Affiliation:

1. Department of Orthopaedics , Faculty of Medicine,

2. Juntendo University, Tokyo, Japan , Faculty of Medicine,

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

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

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

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

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

Abstract

Abstract 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 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 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.

Funder

Renee Medical Corporation

Okinaka Memorial Institute for Medical Research

Juntendo University School of Medicine Project grant

Japan Society for the Promotion of Science

Publisher

Oxford University Press (OUP)

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