Prognostic value of blood-based fibrosis biomarkers in patients with metastatic colorectal cancer receiving chemotherapy and bevacizumab

Abstract A desmoplastic colorectal cancer stroma, characterized by excess turnover of the cancer-associated fibroblast derived collagens type III and VI, can lead to reduced drug-uptake and poor treatment response. We investigated the association between biomarkers of collagen type III and VI and ov...

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Autores principales:	Neel I. Nissen, Stephanie Kehlet, Mogens K. Boisen, Maria Liljefors, Christina Jensen, Astrid Z. Johansen, Julia S. Johansen, Janine T. Erler, Morten Karsdal, Joachim H. Mortensen, Anette Høye, Nicholas Willumsen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6976c8000d604bf1872674bfffb96a35
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spelling	oai:doaj.org-article:6976c8000d604bf1872674bfffb96a352021-12-02T14:01:21ZPrognostic value of blood-based fibrosis biomarkers in patients with metastatic colorectal cancer receiving chemotherapy and bevacizumab10.1038/s41598-020-79608-02045-2322https://doaj.org/article/6976c8000d604bf1872674bfffb96a352021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79608-0https://doaj.org/toc/2045-2322Abstract A desmoplastic colorectal cancer stroma, characterized by excess turnover of the cancer-associated fibroblast derived collagens type III and VI, can lead to reduced drug-uptake and poor treatment response. We investigated the association between biomarkers of collagen type III and VI and overall survival (OS) in patients with metastatic colorectal cancer (mCRC). Serum samples were collected from 252 patients with mCRC prior to treatment with bevacizumab and chemotherapy. Serum concentrations of biomarkers reflecting formation of collagen type III (PRO-C3) and VI (PRO-C6) and degradation of collagen type VI (C6M and C6Mα3) were determined by ELISA. The biomarkers were evaluated for associations with OS, individually, combined, and after adjusting for carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH) and performance status (PS). High baseline levels (> median) of each collagen biomarker were significantly associated with shorter OS (PRO-C3: HR = 2.0, 95%CI = 1.54–2.63; PRO-C6: HR = 1.6, 95%CI = 1.24–2.11; C6M: HR = 1.4, 95%CI = 1.05–1.78; C6Mα3: HR = 1.6, 95%CI = 1.16–2.07). PRO-C3 and PRO-C6 remained significant after adjustment for CEA, LDH and PS. Weak correlations were seen between the collagen biomarkers (r = 0.03–0.59) and combining all improved prognostic capacity (HR = 3.6, 95%CI = 2.30–5.76). Collagen biomarkers were predictive of shorter OS in patients with mCRC. This supports that collagen- and CAF biology is important in CRC.Neel I. NissenStephanie KehletMogens K. BoisenMaria LiljeforsChristina JensenAstrid Z. JohansenJulia S. JohansenJanine T. ErlerMorten KarsdalJoachim H. MortensenAnette HøyeNicholas WillumsenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Neel I. Nissen Stephanie Kehlet Mogens K. Boisen Maria Liljefors Christina Jensen Astrid Z. Johansen Julia S. Johansen Janine T. Erler Morten Karsdal Joachim H. Mortensen Anette Høye Nicholas Willumsen Prognostic value of blood-based fibrosis biomarkers in patients with metastatic colorectal cancer receiving chemotherapy and bevacizumab
description	Abstract A desmoplastic colorectal cancer stroma, characterized by excess turnover of the cancer-associated fibroblast derived collagens type III and VI, can lead to reduced drug-uptake and poor treatment response. We investigated the association between biomarkers of collagen type III and VI and overall survival (OS) in patients with metastatic colorectal cancer (mCRC). Serum samples were collected from 252 patients with mCRC prior to treatment with bevacizumab and chemotherapy. Serum concentrations of biomarkers reflecting formation of collagen type III (PRO-C3) and VI (PRO-C6) and degradation of collagen type VI (C6M and C6Mα3) were determined by ELISA. The biomarkers were evaluated for associations with OS, individually, combined, and after adjusting for carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH) and performance status (PS). High baseline levels (> median) of each collagen biomarker were significantly associated with shorter OS (PRO-C3: HR = 2.0, 95%CI = 1.54–2.63; PRO-C6: HR = 1.6, 95%CI = 1.24–2.11; C6M: HR = 1.4, 95%CI = 1.05–1.78; C6Mα3: HR = 1.6, 95%CI = 1.16–2.07). PRO-C3 and PRO-C6 remained significant after adjustment for CEA, LDH and PS. Weak correlations were seen between the collagen biomarkers (r = 0.03–0.59) and combining all improved prognostic capacity (HR = 3.6, 95%CI = 2.30–5.76). Collagen biomarkers were predictive of shorter OS in patients with mCRC. This supports that collagen- and CAF biology is important in CRC.
format	article
author	Neel I. Nissen Stephanie Kehlet Mogens K. Boisen Maria Liljefors Christina Jensen Astrid Z. Johansen Julia S. Johansen Janine T. Erler Morten Karsdal Joachim H. Mortensen Anette Høye Nicholas Willumsen
author_facet	Neel I. Nissen Stephanie Kehlet Mogens K. Boisen Maria Liljefors Christina Jensen Astrid Z. Johansen Julia S. Johansen Janine T. Erler Morten Karsdal Joachim H. Mortensen Anette Høye Nicholas Willumsen
author_sort	Neel I. Nissen
title	Prognostic value of blood-based fibrosis biomarkers in patients with metastatic colorectal cancer receiving chemotherapy and bevacizumab
title_short	Prognostic value of blood-based fibrosis biomarkers in patients with metastatic colorectal cancer receiving chemotherapy and bevacizumab
title_full	Prognostic value of blood-based fibrosis biomarkers in patients with metastatic colorectal cancer receiving chemotherapy and bevacizumab
title_fullStr	Prognostic value of blood-based fibrosis biomarkers in patients with metastatic colorectal cancer receiving chemotherapy and bevacizumab
title_full_unstemmed	Prognostic value of blood-based fibrosis biomarkers in patients with metastatic colorectal cancer receiving chemotherapy and bevacizumab
title_sort	prognostic value of blood-based fibrosis biomarkers in patients with metastatic colorectal cancer receiving chemotherapy and bevacizumab
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6976c8000d604bf1872674bfffb96a35
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Prognostic value of blood-based fibrosis biomarkers in patients with metastatic colorectal cancer receiving chemotherapy and bevacizumab

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