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

Anna M Blom; Chrysostomi Gialeli; Catharina Hagerling; Jonna Berntsson; Karin Jirström; Konstantinos S Papadakos

doi:10.3389/fimmu.2023.1167659

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

Front Immunol. 2023 May 3:14:1167659. doi: 10.3389/fimmu.2023.1167659. eCollection 2023.

Authors

Anna M Blom¹, Chrysostomi Gialeli², Catharina Hagerling³, Jonna Berntsson⁴, Karin Jirström⁴, Konstantinos S Papadakos¹

Affiliations

¹ Division of Medical Protein Chemistry, Department of Translational Medicine, Lund University, Malmö, Sweden.
² Cardiovascular Research - Translational Studies, Department of Clinical Sciences, Lund University, Malmö, Sweden.
³ Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden.
⁴ Oncology and Therapeutic Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.

Abstract

Introduction: Cartilage 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.

Methods: Immunohistochemistry 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.

Results: COMP 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.

Discussion: The 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.

Keywords: Cartilage Oligomeric Matrix Protein (COMP); PD-L1; T-cells; collagen; colon cancer; fibrosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

B7-H1 Antigen* / metabolism
Biomarkers
Cartilage Oligomeric Matrix Protein* / metabolism
Colorectal Neoplasms*
Humans
Prognosis

Substances

B7-H1 Antigen
Biomarkers
Cartilage Oligomeric Matrix Protein
COMP protein, human

Grants and funding

This study was supported by the Swedish Cancer Society, the Erling-Persson Foundation, Malmö Hospital Cancer Foundation, and the governmental grant for clinical research (ALF).