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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-020-79608-0 |
| _version_ | 1818429181660233728 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T15:13:26Z |
| format | Article |
| id | doaj.art-6976c8000d604bf1872674bfffb96a35 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T15:13:26Z |
| publishDate | 2021-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-6976c8000d604bf1872674bfffb96a352022-12-21T22:56:27ZengNature PortfolioScientific Reports2045-23222021-01-0111111210.1038/s41598-020-79608-0Prognostic value of blood-based fibrosis biomarkers in patients with metastatic colorectal cancer receiving chemotherapy and bevacizumabNeel I. Nissen0Stephanie Kehlet1Mogens K. Boisen2Maria Liljefors3Christina Jensen4Astrid Z. Johansen5Julia S. Johansen6Janine T. Erler7Morten Karsdal8Joachim H. Mortensen9Anette Høye10Nicholas Willumsen11Biotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH)Biomarkers and Research, Nordic BioscienceDepartment of Oncology, Herlev and Gentofte Hospital, Copenhagen University HospitalDepartment of Clinical Science, Intervention and Technology, Karolinska University Hospital HuddingeBiomarkers and Research, Nordic BioscienceDepartment of Oncology, Herlev and Gentofte Hospital, Copenhagen University HospitalDepartment of Oncology, Herlev and Gentofte Hospital, Copenhagen University HospitalBiotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH)Biomarkers and Research, Nordic BioscienceBiomarkers and Research, Nordic BioscienceBiotech Research and Innovation Centre (BRIC), University of Copenhagen (UCPH)Biomarkers and Research, Nordic BioscienceAbstract 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.https://doi.org/10.1038/s41598-020-79608-0 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-020-79608-0 |
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