Expression of Cartilage Oligomeric Matrix Protein in colorectal cancer is an adverse prognostic factor and correlates negatively with infiltrating immune cells and PD-L1 expression

IntroductionCartilage Oligomeric Matrix Protein (COMP) is an oncogenic protein that has been associated with a decrease in infiltrating T-cells in periampullary adenocarcinoma. This study aimed to investigate whether this is also the case for colorectal cancer (CRC) and to evaluate the relationship...

Full description

Bibliographic Details
Main Authors: Anna M. Blom, Chrysostomi Gialeli, Catharina Hagerling, Jonna Berntsson, Karin Jirström, Konstantinos S. Papadakos
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-05-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1167659/full
_version_ 1827955191782047744
author Anna M. Blom
Chrysostomi Gialeli
Catharina Hagerling
Jonna Berntsson
Karin Jirström
Konstantinos S. Papadakos
author_facet Anna M. Blom
Chrysostomi Gialeli
Catharina Hagerling
Jonna Berntsson
Karin Jirström
Konstantinos S. Papadakos
author_sort Anna M. Blom
collection DOAJ
description IntroductionCartilage Oligomeric Matrix Protein (COMP) is an oncogenic protein that has been associated with a decrease in infiltrating T-cells in periampullary adenocarcinoma. This study aimed to investigate whether this is also the case for colorectal cancer (CRC) and to evaluate the relationship between COMP expression and clinopathological features.MethodsImmunohistochemistry was used to determine the expression levels of COMP in tumor cells and stroma in primary tumors from a cohort of 537 CRC patients. The expression of immune cell markers, including CD3+, CD8+, FoxP3+, CD68+, CD56+, CD163+, and PD-L1, was evaluated previously. Tumor fibrosis was assessed by Sirius Red staining and evaluation of collagen fiber organization.ResultsCOMP expression correlated positively with TNM-stage and grade of differentiation. Patients with CRC expressing high levels of COMP had significantly shorter OS than those with low COMP expression (p<0.0001), and fewer infiltrating T-cells were detected in tumors with high COMP expression. Additionally, a negative correlation was identified between the expression of COMP and PD-L1 on both tumor cells and immune cells. Cox regression analysis showed that tumors expressing high levels of COMP had significantly shorter OS, independent of all evaluated immune cell markers. Tumor fibrosis was correlated with high expression of COMP in the stroma (p<0.0001), and tumors with high levels of COMP expression and denser fibrosis displayed more sparse immune cell infiltration.DiscussionThe results suggest that COMP expression in CRC may exert an immune regulatory effect by increasing dense fibrosis and decreasing immune cell infiltration. These findings support the notion that COMP is an important factor in the development and progression of CRC.
first_indexed 2024-04-09T14:41:59Z
format Article
id doaj.art-196d7d38f38b48b7aa5ea66fe6f0bbaf
institution Directory Open Access Journal
issn 1664-3224
language English
last_indexed 2024-04-09T14:41:59Z
publishDate 2023-05-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj.art-196d7d38f38b48b7aa5ea66fe6f0bbaf2023-05-03T05:24:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-05-011410.3389/fimmu.2023.11676591167659Expression of Cartilage Oligomeric Matrix Protein in colorectal cancer is an adverse prognostic factor and correlates negatively with infiltrating immune cells and PD-L1 expressionAnna M. Blom0Chrysostomi Gialeli1Catharina Hagerling2Jonna Berntsson3Karin Jirström4Konstantinos S. Papadakos5Division of Medical Protein Chemistry, Department of Translational Medicine, Lund University, Malmö, SwedenCardiovascular Research - Translational Studies, Department of Clinical Sciences, Lund University, Malmö, SwedenDivision of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, SwedenOncology and Therapeutic Pathology, Department of Clinical Sciences Lund, Lund University, Lund, SwedenOncology and Therapeutic Pathology, Department of Clinical Sciences Lund, Lund University, Lund, SwedenDivision of Medical Protein Chemistry, Department of Translational Medicine, Lund University, Malmö, SwedenIntroductionCartilage Oligomeric Matrix Protein (COMP) is an oncogenic protein that has been associated with a decrease in infiltrating T-cells in periampullary adenocarcinoma. This study aimed to investigate whether this is also the case for colorectal cancer (CRC) and to evaluate the relationship between COMP expression and clinopathological features.MethodsImmunohistochemistry was used to determine the expression levels of COMP in tumor cells and stroma in primary tumors from a cohort of 537 CRC patients. The expression of immune cell markers, including CD3+, CD8+, FoxP3+, CD68+, CD56+, CD163+, and PD-L1, was evaluated previously. Tumor fibrosis was assessed by Sirius Red staining and evaluation of collagen fiber organization.ResultsCOMP expression correlated positively with TNM-stage and grade of differentiation. Patients with CRC expressing high levels of COMP had significantly shorter OS than those with low COMP expression (p<0.0001), and fewer infiltrating T-cells were detected in tumors with high COMP expression. Additionally, a negative correlation was identified between the expression of COMP and PD-L1 on both tumor cells and immune cells. Cox regression analysis showed that tumors expressing high levels of COMP had significantly shorter OS, independent of all evaluated immune cell markers. Tumor fibrosis was correlated with high expression of COMP in the stroma (p<0.0001), and tumors with high levels of COMP expression and denser fibrosis displayed more sparse immune cell infiltration.DiscussionThe results suggest that COMP expression in CRC may exert an immune regulatory effect by increasing dense fibrosis and decreasing immune cell infiltration. These findings support the notion that COMP is an important factor in the development and progression of CRC.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1167659/fullcolon cancerT-cellsPD-L1collagenfibrosisCartilage Oligomeric Matrix Protein (COMP)
spellingShingle Anna M. Blom
Chrysostomi Gialeli
Catharina Hagerling
Jonna Berntsson
Karin Jirström
Konstantinos S. Papadakos
Expression of Cartilage Oligomeric Matrix Protein in colorectal cancer is an adverse prognostic factor and correlates negatively with infiltrating immune cells and PD-L1 expression
Frontiers in Immunology
colon cancer
T-cells
PD-L1
collagen
fibrosis
Cartilage Oligomeric Matrix Protein (COMP)
title Expression of Cartilage Oligomeric Matrix Protein in colorectal cancer is an adverse prognostic factor and correlates negatively with infiltrating immune cells and PD-L1 expression
title_full Expression of Cartilage Oligomeric Matrix Protein in colorectal cancer is an adverse prognostic factor and correlates negatively with infiltrating immune cells and PD-L1 expression
title_fullStr Expression of Cartilage Oligomeric Matrix Protein in colorectal cancer is an adverse prognostic factor and correlates negatively with infiltrating immune cells and PD-L1 expression
title_full_unstemmed Expression of Cartilage Oligomeric Matrix Protein in colorectal cancer is an adverse prognostic factor and correlates negatively with infiltrating immune cells and PD-L1 expression
title_short Expression of Cartilage Oligomeric Matrix Protein in colorectal cancer is an adverse prognostic factor and correlates negatively with infiltrating immune cells and PD-L1 expression
title_sort expression of cartilage oligomeric matrix protein in colorectal cancer is an adverse prognostic factor and correlates negatively with infiltrating immune cells and pd l1 expression
topic colon cancer
T-cells
PD-L1
collagen
fibrosis
Cartilage Oligomeric Matrix Protein (COMP)
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1167659/full
work_keys_str_mv AT annamblom expressionofcartilageoligomericmatrixproteinincolorectalcancerisanadverseprognosticfactorandcorrelatesnegativelywithinfiltratingimmunecellsandpdl1expression
AT chrysostomigialeli expressionofcartilageoligomericmatrixproteinincolorectalcancerisanadverseprognosticfactorandcorrelatesnegativelywithinfiltratingimmunecellsandpdl1expression
AT catharinahagerling expressionofcartilageoligomericmatrixproteinincolorectalcancerisanadverseprognosticfactorandcorrelatesnegativelywithinfiltratingimmunecellsandpdl1expression
AT jonnaberntsson expressionofcartilageoligomericmatrixproteinincolorectalcancerisanadverseprognosticfactorandcorrelatesnegativelywithinfiltratingimmunecellsandpdl1expression
AT karinjirstrom expressionofcartilageoligomericmatrixproteinincolorectalcancerisanadverseprognosticfactorandcorrelatesnegativelywithinfiltratingimmunecellsandpdl1expression
AT konstantinosspapadakos expressionofcartilageoligomericmatrixproteinincolorectalcancerisanadverseprognosticfactorandcorrelatesnegativelywithinfiltratingimmunecellsandpdl1expression