Cargando…

Autoreactivity against Denatured Type III Collagen Is Significantly Decreased in Serum from Patients with Cancer Compared to Healthy Controls

Autoantibodies have the potential as cancer biomarkers as they may associate with the outcome and immune-related adverse events (irAEs) following immunotherapy. Cancer and other fibroinflammatory diseases, such as rheumatoid arthritis (RA), are associated with excessive collagen turnover leading to...

Descripción completa

Detalles Bibliográficos
Autores principales: Jensen, Christina, Drobinski, Patryk, Thorlacius-Ussing, Jeppe, Karsdal, Morten A., Bay-Jensen, Anne-Christine, Willumsen, Nicholas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10139183/
https://www.ncbi.nlm.nih.gov/pubmed/37108227
http://dx.doi.org/10.3390/ijms24087067
_version_ 1785032885482291200
author Jensen, Christina
Drobinski, Patryk
Thorlacius-Ussing, Jeppe
Karsdal, Morten A.
Bay-Jensen, Anne-Christine
Willumsen, Nicholas
author_facet Jensen, Christina
Drobinski, Patryk
Thorlacius-Ussing, Jeppe
Karsdal, Morten A.
Bay-Jensen, Anne-Christine
Willumsen, Nicholas
author_sort Jensen, Christina
collection PubMed
description Autoantibodies have the potential as cancer biomarkers as they may associate with the outcome and immune-related adverse events (irAEs) following immunotherapy. Cancer and other fibroinflammatory diseases, such as rheumatoid arthritis (RA), are associated with excessive collagen turnover leading to collagen triple helix unfolding and denaturation with exposure of immunodominant epitopes. In this study, we aimed to investigate the role of autoreactivity against denatured collagen in cancer. A technically robust assay to quantify autoantibodies against denatured type III collagen products (anti-dCol3) was developed and then measured in pretreatment serum from 223 cancer patients and 33 age-matched controls. Moreover, the association between anti-dCol3 levels and type III collagen degradation (C3M) and formation (PRO-C3) was investigated. Anti-dCol3 levels were significantly lower in patients with bladder (p = 0.0007), breast (p = 0.0002), colorectal (p < 0.0001), head and neck (p = 0.0005), kidney (p = 0.005), liver (p = 0.030), lung (p = 0.0004), melanoma (p < 0.0001), ovarian (p < 0.0001), pancreatic (p < 0.0001), prostate (p < 0.0001), and stomach cancers (p < 0.0001) compared to controls. High anti-dCol3 levels were associated with type III collagen degradation (C3M, p = 0.0002) but not type III collagen formation (PRO-C3, p = 0.26). Cancer patients with different solid tumor types have downregulated levels of circulating autoantibodies against denatured type III collagen compared to controls, suggesting that autoreactivity against unhealthy type III collagen may be important for tumor control and eradication. This autoimmunity biomarker may have the potential for studying the close relationship between autoimmunity and cancer.
format Online
Article
Text
id pubmed-10139183
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-101391832023-04-28 Autoreactivity against Denatured Type III Collagen Is Significantly Decreased in Serum from Patients with Cancer Compared to Healthy Controls Jensen, Christina Drobinski, Patryk Thorlacius-Ussing, Jeppe Karsdal, Morten A. Bay-Jensen, Anne-Christine Willumsen, Nicholas Int J Mol Sci Article Autoantibodies have the potential as cancer biomarkers as they may associate with the outcome and immune-related adverse events (irAEs) following immunotherapy. Cancer and other fibroinflammatory diseases, such as rheumatoid arthritis (RA), are associated with excessive collagen turnover leading to collagen triple helix unfolding and denaturation with exposure of immunodominant epitopes. In this study, we aimed to investigate the role of autoreactivity against denatured collagen in cancer. A technically robust assay to quantify autoantibodies against denatured type III collagen products (anti-dCol3) was developed and then measured in pretreatment serum from 223 cancer patients and 33 age-matched controls. Moreover, the association between anti-dCol3 levels and type III collagen degradation (C3M) and formation (PRO-C3) was investigated. Anti-dCol3 levels were significantly lower in patients with bladder (p = 0.0007), breast (p = 0.0002), colorectal (p < 0.0001), head and neck (p = 0.0005), kidney (p = 0.005), liver (p = 0.030), lung (p = 0.0004), melanoma (p < 0.0001), ovarian (p < 0.0001), pancreatic (p < 0.0001), prostate (p < 0.0001), and stomach cancers (p < 0.0001) compared to controls. High anti-dCol3 levels were associated with type III collagen degradation (C3M, p = 0.0002) but not type III collagen formation (PRO-C3, p = 0.26). Cancer patients with different solid tumor types have downregulated levels of circulating autoantibodies against denatured type III collagen compared to controls, suggesting that autoreactivity against unhealthy type III collagen may be important for tumor control and eradication. This autoimmunity biomarker may have the potential for studying the close relationship between autoimmunity and cancer. MDPI 2023-04-11 /pmc/articles/PMC10139183/ /pubmed/37108227 http://dx.doi.org/10.3390/ijms24087067 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jensen, Christina
Drobinski, Patryk
Thorlacius-Ussing, Jeppe
Karsdal, Morten A.
Bay-Jensen, Anne-Christine
Willumsen, Nicholas
Autoreactivity against Denatured Type III Collagen Is Significantly Decreased in Serum from Patients with Cancer Compared to Healthy Controls
title Autoreactivity against Denatured Type III Collagen Is Significantly Decreased in Serum from Patients with Cancer Compared to Healthy Controls
title_full Autoreactivity against Denatured Type III Collagen Is Significantly Decreased in Serum from Patients with Cancer Compared to Healthy Controls
title_fullStr Autoreactivity against Denatured Type III Collagen Is Significantly Decreased in Serum from Patients with Cancer Compared to Healthy Controls
title_full_unstemmed Autoreactivity against Denatured Type III Collagen Is Significantly Decreased in Serum from Patients with Cancer Compared to Healthy Controls
title_short Autoreactivity against Denatured Type III Collagen Is Significantly Decreased in Serum from Patients with Cancer Compared to Healthy Controls
title_sort autoreactivity against denatured type iii collagen is significantly decreased in serum from patients with cancer compared to healthy controls
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10139183/
https://www.ncbi.nlm.nih.gov/pubmed/37108227
http://dx.doi.org/10.3390/ijms24087067
work_keys_str_mv AT jensenchristina autoreactivityagainstdenaturedtypeiiicollagenissignificantlydecreasedinserumfrompatientswithcancercomparedtohealthycontrols
AT drobinskipatryk autoreactivityagainstdenaturedtypeiiicollagenissignificantlydecreasedinserumfrompatientswithcancercomparedtohealthycontrols
AT thorlaciusussingjeppe autoreactivityagainstdenaturedtypeiiicollagenissignificantlydecreasedinserumfrompatientswithcancercomparedtohealthycontrols
AT karsdalmortena autoreactivityagainstdenaturedtypeiiicollagenissignificantlydecreasedinserumfrompatientswithcancercomparedtohealthycontrols
AT bayjensenannechristine autoreactivityagainstdenaturedtypeiiicollagenissignificantlydecreasedinserumfrompatientswithcancercomparedtohealthycontrols
AT willumsennicholas autoreactivityagainstdenaturedtypeiiicollagenissignificantlydecreasedinserumfrompatientswithcancercomparedtohealthycontrols