Type XXII Collagen Complements Fibrillar Collagens in the Serological Assessment of Tumor Fibrosis and the Outcome in Pancreatic Cancer
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...
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MDPI AG
2022-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/23/3763 |
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| author | Emilie A. Madsen Jeppe Thorlacius-Ussing Neel I. Nissen Christina Jensen Inna M. Chen Julia S. Johansen Hadi M. H. Diab Lars N. Jørgensen Carsten P. Hansen Morten A. Karsdal Nicholas Willumsen |
| author_facet | Emilie A. Madsen Jeppe Thorlacius-Ussing Neel I. Nissen Christina Jensen Inna M. Chen Julia S. Johansen Hadi M. H. Diab Lars N. Jørgensen Carsten P. Hansen Morten A. Karsdal Nicholas Willumsen |
| author_sort | Emilie A. Madsen |
| collection | DOAJ |
| description | 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 (<i>p</i> < 0.01 to <i>p</i> < 0.0001), and the diagnostic accuracy (AUROC) ranged from 0.87 to 0.98, <i>p</i> < 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, <i>p</i> = 0.0006) and this remained significant after adjusting for PRO-C3 (HR = 4.27, 95% CI 1.24–10.4, <i>p</i> = 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. |
| first_indexed | 2024-03-09T17:51:15Z |
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| id | doaj.art-46a77022ccbd47e297ef2d33349a1417 |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T17:51:15Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-46a77022ccbd47e297ef2d33349a14172023-11-24T10:43:25ZengMDPI AGCells2073-44092022-11-011123376310.3390/cells11233763Type XXII Collagen Complements Fibrillar Collagens in the Serological Assessment of Tumor Fibrosis and the Outcome in Pancreatic CancerEmilie A. Madsen0Jeppe Thorlacius-Ussing1Neel I. Nissen2Christina Jensen3Inna M. Chen4Julia S. Johansen5Hadi M. H. Diab6Lars N. Jørgensen7Carsten P. Hansen8Morten A. Karsdal9Nicholas Willumsen10Biomarkers and Research, Nordic Bioscience A/S, Herlev Hovedgade 207, 2730 Herlev, DenmarkBiomarkers and Research, Nordic Bioscience A/S, Herlev Hovedgade 207, 2730 Herlev, DenmarkBiomarkers and Research, Nordic Bioscience A/S, Herlev Hovedgade 207, 2730 Herlev, DenmarkBiomarkers and Research, Nordic Bioscience A/S, Herlev Hovedgade 207, 2730 Herlev, DenmarkDepartment of Oncology, Copenhagen University Hospital—Herlev and Gentofte, 2730 Herlev, DenmarkDepartment of Oncology, Copenhagen University Hospital—Herlev and Gentofte, 2730 Herlev, DenmarkDigestive Disease Center, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen, DenmarkDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, DenmarkDepartment of Surgery, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, DenmarkBiomarkers and Research, Nordic Bioscience A/S, Herlev Hovedgade 207, 2730 Herlev, DenmarkBiomarkers and Research, Nordic Bioscience A/S, Herlev Hovedgade 207, 2730 Herlev, DenmarkCirculating 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 (<i>p</i> < 0.01 to <i>p</i> < 0.0001), and the diagnostic accuracy (AUROC) ranged from 0.87 to 0.98, <i>p</i> < 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, <i>p</i> = 0.0006) and this remained significant after adjusting for PRO-C3 (HR = 4.27, 95% CI 1.24–10.4, <i>p</i> = 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.https://www.mdpi.com/2073-4409/11/23/3763collagensECMnon-invasive biomarkerPDACtumor fibrosistype XXII collagen |
| spellingShingle | Emilie A. Madsen Jeppe Thorlacius-Ussing Neel I. Nissen Christina Jensen Inna M. Chen Julia S. Johansen Hadi M. H. Diab Lars N. Jørgensen Carsten P. Hansen Morten A. Karsdal Nicholas Willumsen Type XXII Collagen Complements Fibrillar Collagens in the Serological Assessment of Tumor Fibrosis and the Outcome in Pancreatic Cancer Cells collagens ECM non-invasive biomarker PDAC tumor fibrosis type XXII collagen |
| title | Type XXII Collagen Complements Fibrillar Collagens in the Serological Assessment of Tumor Fibrosis and the Outcome in Pancreatic Cancer |
| title_full | Type XXII Collagen Complements Fibrillar Collagens in the Serological Assessment of Tumor Fibrosis and the Outcome in Pancreatic Cancer |
| title_fullStr | Type XXII Collagen Complements Fibrillar Collagens in the Serological Assessment of Tumor Fibrosis and the Outcome in Pancreatic Cancer |
| title_full_unstemmed | Type XXII Collagen Complements Fibrillar Collagens in the Serological Assessment of Tumor Fibrosis and the Outcome in Pancreatic Cancer |
| title_short | Type XXII Collagen Complements Fibrillar Collagens in the Serological Assessment of Tumor Fibrosis and the Outcome in Pancreatic Cancer |
| title_sort | type xxii collagen complements fibrillar collagens in the serological assessment of tumor fibrosis and the outcome in pancreatic cancer |
| topic | collagens ECM non-invasive biomarker PDAC tumor fibrosis type XXII collagen |
| url | https://www.mdpi.com/2073-4409/11/23/3763 |
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