Type XXII Collagen Complements Fibrillar Collagens in the Serological Assessment of Tumor Fibrosis and the Outcome in Pancreatic Cancer
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Type XXII Collagen Complements Fibrillar Collagens in the Serological Assessment of Tumor Fibrosis and the Outcome in Pancreatic Cancer. / Madsen, Emilie A.; Thorlacius-Ussing, Jeppe; Nissen, Neel I.; Jensen, Christina; Chen, Inna M.; Johansen, Julia S.; Diab, Hadi M.H.; Jørgensen, Lars N.; Hansen, Carsten P.; Karsdal, Morten A.; Willumsen, Nicholas.
I: Cells, Bind 11, Nr. 23, 3763, 2022.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Type XXII Collagen Complements Fibrillar Collagens in the Serological Assessment of Tumor Fibrosis and the Outcome in Pancreatic Cancer
AU - Madsen, Emilie A.
AU - Thorlacius-Ussing, Jeppe
AU - Nissen, Neel I.
AU - Jensen, Christina
AU - Chen, Inna M.
AU - Johansen, Julia S.
AU - Diab, Hadi M.H.
AU - Jørgensen, Lars N.
AU - Hansen, Carsten P.
AU - Karsdal, Morten A.
AU - Willumsen, Nicholas
N1 - Publisher Copyright: © 2022 by the authors.
PY - 2022
Y1 - 2022
N2 - Circulating fragments of type III collagen, measured by PRO-C3, has shown promising results as a tumor fibrosis biomarker. However, the fibrotic tumor microenvironment consists of many other collagens with diverse functions and unexplored biomarker potential. One example hereof is type XXII collagen (COL22). In this study, we investigated the biomarker potential of COL22 by measuring this in serum. An ELISA, named PRO-C22, was developed and measured in two serum cohorts consisting of patients with various solid tumors (n = 220) and healthy subjects (n = 33) (Cohort 1), and patients with pancreatic ductal adenocarcinoma (PDAC) (n = 34), and healthy subjects (n = 20) (Cohort 2). In Cohort 1, PRO-C22 was elevated in the serum from patients with solid tumors, compared to healthy subjects (p < 0.01 to p < 0.0001), and the diagnostic accuracy (AUROC) ranged from 0.87 to 0.98, p < 0.0001. In Cohort 2, the high levels of PRO-C22, in patients with PDAC, were predictive of a worse overall survival (HR = 4.52, 95% CI 1.90–10.7, p = 0.0006) and this remained significant after adjusting for PRO-C3 (HR = 4.27, 95% CI 1.24–10.4, p = 0.0013). In conclusion, PRO-C22 has diagnostic biomarker potential in various solid tumor types and prognostic biomarker potential in PDAC. Furthermore, PRO-C22 complemented PRO-C3 in predicting mortality, suggesting an additive prognostic value when quantifying different collagens.
AB - Circulating fragments of type III collagen, measured by PRO-C3, has shown promising results as a tumor fibrosis biomarker. However, the fibrotic tumor microenvironment consists of many other collagens with diverse functions and unexplored biomarker potential. One example hereof is type XXII collagen (COL22). In this study, we investigated the biomarker potential of COL22 by measuring this in serum. An ELISA, named PRO-C22, was developed and measured in two serum cohorts consisting of patients with various solid tumors (n = 220) and healthy subjects (n = 33) (Cohort 1), and patients with pancreatic ductal adenocarcinoma (PDAC) (n = 34), and healthy subjects (n = 20) (Cohort 2). In Cohort 1, PRO-C22 was elevated in the serum from patients with solid tumors, compared to healthy subjects (p < 0.01 to p < 0.0001), and the diagnostic accuracy (AUROC) ranged from 0.87 to 0.98, p < 0.0001. In Cohort 2, the high levels of PRO-C22, in patients with PDAC, were predictive of a worse overall survival (HR = 4.52, 95% CI 1.90–10.7, p = 0.0006) and this remained significant after adjusting for PRO-C3 (HR = 4.27, 95% CI 1.24–10.4, p = 0.0013). In conclusion, PRO-C22 has diagnostic biomarker potential in various solid tumor types and prognostic biomarker potential in PDAC. Furthermore, PRO-C22 complemented PRO-C3 in predicting mortality, suggesting an additive prognostic value when quantifying different collagens.
KW - collagens
KW - ECM
KW - non-invasive biomarker
KW - PDAC
KW - tumor fibrosis
KW - type XXII collagen
U2 - 10.3390/cells11233763
DO - 10.3390/cells11233763
M3 - Journal article
C2 - 36497023
AN - SCOPUS:85143623674
VL - 11
JO - Cells
JF - Cells
SN - 2073-4409
IS - 23
M1 - 3763
ER -
ID: 329571780