CD163 as a Biomarker in Colorectal Cancer: The Expression on Circulating Monocytes and Tumor-Associated Macrophages, and the Soluble Form in the Blood

The macrophage-associated molecule CD163 has been reported as a prognostic biomarker in different cancer types, but its role in colorectal cancer (CRC) is unclear. We studied CD163 in the tumor microenvironment and circulation of patients with CRC in relation to clinicopathological parameters. An en...

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Main Authors: Daniëlle Krijgsman, Natasja L. De Vries, Morten N. Andersen, Anni Skovbo, Rob A.E.M. Tollenaar, Holger J. Møller, Marianne Hokland, Peter J.K. Kuppen
Format: Article
Language:English
Published: MDPI AG 2020-08-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/21/16/5925
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author Daniëlle Krijgsman
Natasja L. De Vries
Morten N. Andersen
Anni Skovbo
Rob A.E.M. Tollenaar
Holger J. Møller
Marianne Hokland
Peter J.K. Kuppen
author_facet Daniëlle Krijgsman
Natasja L. De Vries
Morten N. Andersen
Anni Skovbo
Rob A.E.M. Tollenaar
Holger J. Møller
Marianne Hokland
Peter J.K. Kuppen
author_sort Daniëlle Krijgsman
collection DOAJ
description The macrophage-associated molecule CD163 has been reported as a prognostic biomarker in different cancer types, but its role in colorectal cancer (CRC) is unclear. We studied CD163 in the tumor microenvironment and circulation of patients with CRC in relation to clinicopathological parameters. An enzyme-linked immunosorbent assay (ELISA) was used to measure the serum sCD163 levels and multiparameter flow cytometry was used to study the peripheral blood monocytes and their CD163 expression in CRC patients (<i>N</i> = 78) and healthy donors (<i>N</i> = 50). The distribution of tumor-associated macrophages (TAMs) was studied in primary colorectal tumors with multiplex immunofluorescence. We showed that CRC patients with above-median sCD163 level had a shorter overall survival (OS, <i>p</i> = 0.035) as well as disease-free survival (DFS, <i>p</i> = 0.005). The above-median sCD163 remained significantly associated with a shorter DFS in the multivariate analysis (<i>p</i> = 0.049). Moreover, a shorter OS was observed in CRC patients with an above-median total monocyte percentage (<i>p</i> = 0.007). The number and phenotype of the stromal and intraepithelial TAMs in colorectal tumors were not associated with clinical outcome. In conclusion, sCD163 and monocytes in the circulation may be potential prognostic biomarkers in CRC patients, whereas TAMs in the tumor showed no association with clinical outcome. Thus, our results emphasize the importance of the innate systemic immune response in CRC disease progression.
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spelling doaj.art-abf8008d136448b99b3ef6cbc991edd72023-11-20T10:28:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012116592510.3390/ijms21165925CD163 as a Biomarker in Colorectal Cancer: The Expression on Circulating Monocytes and Tumor-Associated Macrophages, and the Soluble Form in the BloodDaniëlle Krijgsman0Natasja L. De Vries1Morten N. Andersen2Anni Skovbo3Rob A.E.M. Tollenaar4Holger J. Møller5Marianne Hokland6Peter J.K. Kuppen7Department of Surgery, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The NetherlandsDepartment of Surgery, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The NetherlandsDepartment of Biomedicine, Aarhus University, 8000 Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, 8000 Aarhus, DenmarkDepartment of Surgery, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The NetherlandsDepartment of Clinical Biochemistry, Aarhus University Hospital, 8200 Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, 8000 Aarhus, DenmarkDepartment of Surgery, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The NetherlandsThe macrophage-associated molecule CD163 has been reported as a prognostic biomarker in different cancer types, but its role in colorectal cancer (CRC) is unclear. We studied CD163 in the tumor microenvironment and circulation of patients with CRC in relation to clinicopathological parameters. An enzyme-linked immunosorbent assay (ELISA) was used to measure the serum sCD163 levels and multiparameter flow cytometry was used to study the peripheral blood monocytes and their CD163 expression in CRC patients (<i>N</i> = 78) and healthy donors (<i>N</i> = 50). The distribution of tumor-associated macrophages (TAMs) was studied in primary colorectal tumors with multiplex immunofluorescence. We showed that CRC patients with above-median sCD163 level had a shorter overall survival (OS, <i>p</i> = 0.035) as well as disease-free survival (DFS, <i>p</i> = 0.005). The above-median sCD163 remained significantly associated with a shorter DFS in the multivariate analysis (<i>p</i> = 0.049). Moreover, a shorter OS was observed in CRC patients with an above-median total monocyte percentage (<i>p</i> = 0.007). The number and phenotype of the stromal and intraepithelial TAMs in colorectal tumors were not associated with clinical outcome. In conclusion, sCD163 and monocytes in the circulation may be potential prognostic biomarkers in CRC patients, whereas TAMs in the tumor showed no association with clinical outcome. Thus, our results emphasize the importance of the innate systemic immune response in CRC disease progression.https://www.mdpi.com/1422-0067/21/16/5925colorectal cancerprognostic immune markersmonocytestumor-associated macrophagessoluble CD163regulatory T cells
spellingShingle Daniëlle Krijgsman
Natasja L. De Vries
Morten N. Andersen
Anni Skovbo
Rob A.E.M. Tollenaar
Holger J. Møller
Marianne Hokland
Peter J.K. Kuppen
CD163 as a Biomarker in Colorectal Cancer: The Expression on Circulating Monocytes and Tumor-Associated Macrophages, and the Soluble Form in the Blood
International Journal of Molecular Sciences
colorectal cancer
prognostic immune markers
monocytes
tumor-associated macrophages
soluble CD163
regulatory T cells
title CD163 as a Biomarker in Colorectal Cancer: The Expression on Circulating Monocytes and Tumor-Associated Macrophages, and the Soluble Form in the Blood
title_full CD163 as a Biomarker in Colorectal Cancer: The Expression on Circulating Monocytes and Tumor-Associated Macrophages, and the Soluble Form in the Blood
title_fullStr CD163 as a Biomarker in Colorectal Cancer: The Expression on Circulating Monocytes and Tumor-Associated Macrophages, and the Soluble Form in the Blood
title_full_unstemmed CD163 as a Biomarker in Colorectal Cancer: The Expression on Circulating Monocytes and Tumor-Associated Macrophages, and the Soluble Form in the Blood
title_short CD163 as a Biomarker in Colorectal Cancer: The Expression on Circulating Monocytes and Tumor-Associated Macrophages, and the Soluble Form in the Blood
title_sort cd163 as a biomarker in colorectal cancer the expression on circulating monocytes and tumor associated macrophages and the soluble form in the blood
topic colorectal cancer
prognostic immune markers
monocytes
tumor-associated macrophages
soluble CD163
regulatory T cells
url https://www.mdpi.com/1422-0067/21/16/5925
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