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Systemic and local decorin levels mirror the clinical course of pancreatic cancer

Svensson, Maja LU ; Lehn, Sophie LU ; Jacobsen, Hedda LU ; Olsson Hau, Sofie LU orcid ; Jönsson, Göran LU ; Pietras, Kristian LU orcid and Jirström, Karin LU orcid (2026) In The Journal of Pathology: Clinical Research 12(1).
Abstract

Despite significant progress in oncology research, pancreatic cancer remains inherently difficult to treat, and the mechanisms underlying therapeutic resistance remain unresolved. Decorin (DCN), a member of the family of small leucine-rich proteoglycans, has emerged as a versatile actor in various malignant diseases. The aim of this study was to further explore the potential clinical significance of DCN in pancreatic cancer, both regarding its dynamics in serum during chemotherapy and its compartmental and cellular distribution in tumour tissue. To this end, repeated on-treatment levels of soluble DCN were measured using proximity extension assay in 124 patients enrolled in a prospective, observational clinical study, inviting patients... (More)

Despite significant progress in oncology research, pancreatic cancer remains inherently difficult to treat, and the mechanisms underlying therapeutic resistance remain unresolved. Decorin (DCN), a member of the family of small leucine-rich proteoglycans, has emerged as a versatile actor in various malignant diseases. The aim of this study was to further explore the potential clinical significance of DCN in pancreatic cancer, both regarding its dynamics in serum during chemotherapy and its compartmental and cellular distribution in tumour tissue. To this end, repeated on-treatment levels of soluble DCN were measured using proximity extension assay in 124 patients enrolled in a prospective, observational clinical study, inviting patients diagnosed with pancreatic or other pancreatobiliary-type periampullary adenocarcinoma eligible for adjuvant (n = 30) or first-line palliative (n = 94) chemotherapy. Multiplexed immunofluorescence was applied to map DCN and the associated immune landscape in resected tumours. The results showed increasing levels of DCN in serum after initiation of chemotherapy in palliative, but not in adjuvant, patients. A higher rate of change of serum DCN was an independent adverse prognostic factor in both treatment settings. There was no significant association between systemic levels and local DCN expression. Varying expression of DCN was denoted in both tumour cells, immune cells and stroma, but the prognostic significance was mainly assigned to its expression in B cells. In particular, a higher percentage of DCN positive B cells, overall and in interaction with tumour cells, were independent predictors of shorter survival. In summary, this study is the first to demonstrate the potential clinical utility of on-treatment monitoring of systemic DCN in patients with pancreatic cancer. The findings also provide interesting leads for further research into how DCN may interact with the immune microenvironment to promote tumour development and the emergence of chemoresistance.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Decorin/blood, Pancreatic Neoplasms/pathology, Female, Male, Middle Aged, Aged, Prospective Studies, Biomarkers, Tumor/blood, Tumor Microenvironment, Adenocarcinoma/pathology, Chemotherapy, Adjuvant, Palliative Care, Adult, Aged, 80 and over
in
The Journal of Pathology: Clinical Research
volume
12
issue
1
article number
e70066
publisher
Wiley-Blackwell
external identifiers
  • pmid:41392017
ISSN
2056-4538
DOI
10.1002/2056-4538.70066
project
Chemotherapy, Host response And Molecular dynamics in Periampullary cancer
language
English
LU publication?
yes
additional info
© 2025 The Author(s). The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.
id
32cdc458-ceea-4fd8-ba5c-a43f369e8c0b
date added to LUP
2025-12-15 09:04:40
date last changed
2025-12-15 11:11:46
@article{32cdc458-ceea-4fd8-ba5c-a43f369e8c0b,
  abstract     = {{<p>Despite significant progress in oncology research, pancreatic cancer remains inherently difficult to treat, and the mechanisms underlying therapeutic resistance remain unresolved. Decorin (DCN), a member of the family of small leucine-rich proteoglycans, has emerged as a versatile actor in various malignant diseases. The aim of this study was to further explore the potential clinical significance of DCN in pancreatic cancer, both regarding its dynamics in serum during chemotherapy and its compartmental and cellular distribution in tumour tissue. To this end, repeated on-treatment levels of soluble DCN were measured using proximity extension assay in 124 patients enrolled in a prospective, observational clinical study, inviting patients diagnosed with pancreatic or other pancreatobiliary-type periampullary adenocarcinoma eligible for adjuvant (n = 30) or first-line palliative (n = 94) chemotherapy. Multiplexed immunofluorescence was applied to map DCN and the associated immune landscape in resected tumours. The results showed increasing levels of DCN in serum after initiation of chemotherapy in palliative, but not in adjuvant, patients. A higher rate of change of serum DCN was an independent adverse prognostic factor in both treatment settings. There was no significant association between systemic levels and local DCN expression. Varying expression of DCN was denoted in both tumour cells, immune cells and stroma, but the prognostic significance was mainly assigned to its expression in B cells. In particular, a higher percentage of DCN positive B cells, overall and in interaction with tumour cells, were independent predictors of shorter survival. In summary, this study is the first to demonstrate the potential clinical utility of on-treatment monitoring of systemic DCN in patients with pancreatic cancer. The findings also provide interesting leads for further research into how DCN may interact with the immune microenvironment to promote tumour development and the emergence of chemoresistance.</p>}},
  author       = {{Svensson, Maja and Lehn, Sophie and Jacobsen, Hedda and Olsson Hau, Sofie and Jönsson, Göran and Pietras, Kristian and Jirström, Karin}},
  issn         = {{2056-4538}},
  keywords     = {{Humans; Decorin/blood; Pancreatic Neoplasms/pathology; Female; Male; Middle Aged; Aged; Prospective Studies; Biomarkers, Tumor/blood; Tumor Microenvironment; Adenocarcinoma/pathology; Chemotherapy, Adjuvant; Palliative Care; Adult; Aged, 80 and over}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{The Journal of Pathology: Clinical Research}},
  title        = {{Systemic and local decorin levels mirror the clinical course of pancreatic cancer}},
  url          = {{http://dx.doi.org/10.1002/2056-4538.70066}},
  doi          = {{10.1002/2056-4538.70066}},
  volume       = {{12}},
  year         = {{2026}},
}