TY - JOUR

T1 - Type XX Collagen Is Elevated in Circulation of Patients with Solid Tumors

AU - Thorlacius‐Ussing, Jeppe

AU - Jensen, Christina

AU - Madsen, Emilie A.

AU - Nissen, Neel I.

AU - Manon‐Jensen, Tina

AU - Chen, Inna M.

AU - Johansen, Julia S.

AU - Diab, Hadi M.H.

AU - Jørgensen, Lars N.

AU - Karsdal, Morten A.

AU - Willumsen, Nicholas

N1 - Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022

Y1 - 2022

N2 - In the tumor microenvironment, the extracellular matrix (ECM) has been recognized as an important part of cancer development. The dominant ECM proteins are the 28 types of collagens, each with a unique function in tissue architecture. Type XX collagen, however, is poorly characterized, and little is known about its involvement in cancer. We developed an ELISA quantifying type XX collagen, named PRO‐C20, using a monoclonal antibody raised against the C‐ terminus. PRO‐C20 and PRO‐C1, an ELISA targeting the N‐terminal pro‐peptide of type I collagen, was measured in sera of 219 patients with various solid cancer types and compared to sera levels of 33 healthy controls. PRO‐C20 was subsequently measured in a separate cohort comprising 36 patients with pancreatic ductal adenocarcinoma (PDAC) and compared to 20 healthy controls and 11 patients with chronic pancreatitis. PRO‐C20 was significantly elevated in all cancers tested: bladder, breast, colorectal, head and neck, kidney, lung, melanoma, ovarian, pancreatic, prostate, and stomach cancer (p < 0.01–p < 0.0001). PRO‐C1 was only elevated in patients with ovarian cancer. PRO‐C20 could discriminate between patients and healthy controls with AUROC values ranging from 0.76 to 0.92. Elevated levels were confirmed in a separate cohort of patients with PDAC (p < 0.0001). High PRO‐C20 levels (above 2.57 nM) were predictive of poor survival after adjusting for the presence of metastasis, age, and sex (HR: 4.25, 95% CI: 1.52–11.9, p‐value: 0.006). Circulating type XX collagen is elevated in sera of patients with various types of cancer and has prognostic value in PDAC. If validated, PRO‐C20 may be a novel biomarker for patients with solid tumors and can help understand the ECM biology of cancer.

AB - In the tumor microenvironment, the extracellular matrix (ECM) has been recognized as an important part of cancer development. The dominant ECM proteins are the 28 types of collagens, each with a unique function in tissue architecture. Type XX collagen, however, is poorly characterized, and little is known about its involvement in cancer. We developed an ELISA quantifying type XX collagen, named PRO‐C20, using a monoclonal antibody raised against the C‐ terminus. PRO‐C20 and PRO‐C1, an ELISA targeting the N‐terminal pro‐peptide of type I collagen, was measured in sera of 219 patients with various solid cancer types and compared to sera levels of 33 healthy controls. PRO‐C20 was subsequently measured in a separate cohort comprising 36 patients with pancreatic ductal adenocarcinoma (PDAC) and compared to 20 healthy controls and 11 patients with chronic pancreatitis. PRO‐C20 was significantly elevated in all cancers tested: bladder, breast, colorectal, head and neck, kidney, lung, melanoma, ovarian, pancreatic, prostate, and stomach cancer (p < 0.01–p < 0.0001). PRO‐C1 was only elevated in patients with ovarian cancer. PRO‐C20 could discriminate between patients and healthy controls with AUROC values ranging from 0.76 to 0.92. Elevated levels were confirmed in a separate cohort of patients with PDAC (p < 0.0001). High PRO‐C20 levels (above 2.57 nM) were predictive of poor survival after adjusting for the presence of metastasis, age, and sex (HR: 4.25, 95% CI: 1.52–11.9, p‐value: 0.006). Circulating type XX collagen is elevated in sera of patients with various types of cancer and has prognostic value in PDAC. If validated, PRO‐C20 may be a novel biomarker for patients with solid tumors and can help understand the ECM biology of cancer.

KW - biomarker

KW - cancer

KW - ECM

KW - PDAC

KW - serum

KW - type XX collagen

U2 - 10.3390/ijms23084144

DO - 10.3390/ijms23084144

M3 - Journal article

C2 - 35456962

AN - SCOPUS:85127772173

VL - 23

JO - International Journal of Molecular Sciences (Online)

JF - International Journal of Molecular Sciences (Online)

SN - 1661-6596

IS - 8

M1 - 4144

ER -