Serum type XVI collagen is associated with colorectal cancer and ulcerative colitis indicating a pathological role in gastrointestinal disorders

Christina Jensen*, Signe H. Nielsen, Joachim H. Mortensen, Jens Kjeldsen, Lone G. Klinge, Aleksander Krag, Henrik Harling, Lars N. Jørgensen, Morten A. Karsdal, Nicholas Willumsen

*Corresponding author for this work

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Abstract

Altered extracellular matrix (ECM) remodeling is an important part of the pathology of gastrointestinal (GI) disorders. In the intestine, type XVI collagen (col-16) plays a role in pathogenesis by affecting ECM architecture and induce cell invasion. Measuring col-16 in serum may therefore have biomarker potential in GI disorders such as colorectal cancer (CRC) and ulcerative colitis (UC). The aim of this study was to determine whether col-16 can serve as a biomarker for altered ECM remodeling in patients with CRC and UC. A monoclonal antibody was raised against the C-terminal end of col-16 (PRO-C16), and a competitive enzyme-linked immunosorbent assay (ELISA) was developed and technically validated. Levels of PRO-C16 were measured in serum from patients with CRC (before (n = 50) and 3 months after (n = 23) tumor resections), UC (n = 39) and healthy controls (n = 50). The PRO-C16 ELISA was specific toward the C-terminal of col-16. PRO-C16 was significantly elevated both in serum from patients with CRC (P = 0.0026) and UC (P < 0.0001) compared to controls. No difference was detected in levels of PRO-C16 between patients with CRC at baseline and 3 months after tumor resections (P > 0.999). Levels of PRO-C16 identified patients with a GI disorder with a positive predictive value of 0.9 and an odds ratio of 12 (95%CI = 4.5-29.5, P < 0.0001). The newly developed assay detected significantly elevated levels of PRO-C16 in serum from patients with GI disorders compared to controls suggesting its potential as a biomarker in this setting. Future studies are needed to validate these findings.

Original languageEnglish
JournalCancer Medicine
Volume7
Issue number9
Pages (from-to)4619-4626
ISSN2045-7634
DOIs
Publication statusPublished - 20. Aug 2018

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Ulcerative Colitis
Colorectal Neoplasms
Serum
Intestines
Odds Ratio
Pathology
Neoplasms

Keywords

  • Biomarkers
  • Collagen
  • Colorectal cancer
  • Extracellular matrix
  • Ulcerative colitis

Cite this

Jensen, Christina ; Nielsen, Signe H. ; Mortensen, Joachim H. ; Kjeldsen, Jens ; Klinge, Lone G. ; Krag, Aleksander ; Harling, Henrik ; Jørgensen, Lars N. ; Karsdal, Morten A. ; Willumsen, Nicholas. / Serum type XVI collagen is associated with colorectal cancer and ulcerative colitis indicating a pathological role in gastrointestinal disorders. In: Cancer Medicine. 2018 ; Vol. 7, No. 9. pp. 4619-4626.
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title = "Serum type XVI collagen is associated with colorectal cancer and ulcerative colitis indicating a pathological role in gastrointestinal disorders",
abstract = "Altered extracellular matrix (ECM) remodeling is an important part of the pathology of gastrointestinal (GI) disorders. In the intestine, type XVI collagen (col-16) plays a role in pathogenesis by affecting ECM architecture and induce cell invasion. Measuring col-16 in serum may therefore have biomarker potential in GI disorders such as colorectal cancer (CRC) and ulcerative colitis (UC). The aim of this study was to determine whether col-16 can serve as a biomarker for altered ECM remodeling in patients with CRC and UC. A monoclonal antibody was raised against the C-terminal end of col-16 (PRO-C16), and a competitive enzyme-linked immunosorbent assay (ELISA) was developed and technically validated. Levels of PRO-C16 were measured in serum from patients with CRC (before (n = 50) and 3 months after (n = 23) tumor resections), UC (n = 39) and healthy controls (n = 50). The PRO-C16 ELISA was specific toward the C-terminal of col-16. PRO-C16 was significantly elevated both in serum from patients with CRC (P = 0.0026) and UC (P < 0.0001) compared to controls. No difference was detected in levels of PRO-C16 between patients with CRC at baseline and 3 months after tumor resections (P > 0.999). Levels of PRO-C16 identified patients with a GI disorder with a positive predictive value of 0.9 and an odds ratio of 12 (95{\%}CI = 4.5-29.5, P < 0.0001). The newly developed assay detected significantly elevated levels of PRO-C16 in serum from patients with GI disorders compared to controls suggesting its potential as a biomarker in this setting. Future studies are needed to validate these findings.",
keywords = "Biomarkers, Collagen, Colorectal cancer, Extracellular matrix, Ulcerative colitis",
author = "Christina Jensen and Nielsen, {Signe H.} and Mortensen, {Joachim H.} and Jens Kjeldsen and Klinge, {Lone G.} and Aleksander Krag and Henrik Harling and J{\o}rgensen, {Lars N.} and Karsdal, {Morten A.} and Nicholas Willumsen",
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Serum type XVI collagen is associated with colorectal cancer and ulcerative colitis indicating a pathological role in gastrointestinal disorders. / Jensen, Christina; Nielsen, Signe H.; Mortensen, Joachim H.; Kjeldsen, Jens; Klinge, Lone G.; Krag, Aleksander; Harling, Henrik; Jørgensen, Lars N.; Karsdal, Morten A.; Willumsen, Nicholas.

In: Cancer Medicine, Vol. 7, No. 9, 20.08.2018, p. 4619-4626.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Serum type XVI collagen is associated with colorectal cancer and ulcerative colitis indicating a pathological role in gastrointestinal disorders

AU - Jensen, Christina

AU - Nielsen, Signe H.

AU - Mortensen, Joachim H.

AU - Kjeldsen, Jens

AU - Klinge, Lone G.

AU - Krag, Aleksander

AU - Harling, Henrik

AU - Jørgensen, Lars N.

AU - Karsdal, Morten A.

AU - Willumsen, Nicholas

PY - 2018/8/20

Y1 - 2018/8/20

N2 - Altered extracellular matrix (ECM) remodeling is an important part of the pathology of gastrointestinal (GI) disorders. In the intestine, type XVI collagen (col-16) plays a role in pathogenesis by affecting ECM architecture and induce cell invasion. Measuring col-16 in serum may therefore have biomarker potential in GI disorders such as colorectal cancer (CRC) and ulcerative colitis (UC). The aim of this study was to determine whether col-16 can serve as a biomarker for altered ECM remodeling in patients with CRC and UC. A monoclonal antibody was raised against the C-terminal end of col-16 (PRO-C16), and a competitive enzyme-linked immunosorbent assay (ELISA) was developed and technically validated. Levels of PRO-C16 were measured in serum from patients with CRC (before (n = 50) and 3 months after (n = 23) tumor resections), UC (n = 39) and healthy controls (n = 50). The PRO-C16 ELISA was specific toward the C-terminal of col-16. PRO-C16 was significantly elevated both in serum from patients with CRC (P = 0.0026) and UC (P < 0.0001) compared to controls. No difference was detected in levels of PRO-C16 between patients with CRC at baseline and 3 months after tumor resections (P > 0.999). Levels of PRO-C16 identified patients with a GI disorder with a positive predictive value of 0.9 and an odds ratio of 12 (95%CI = 4.5-29.5, P < 0.0001). The newly developed assay detected significantly elevated levels of PRO-C16 in serum from patients with GI disorders compared to controls suggesting its potential as a biomarker in this setting. Future studies are needed to validate these findings.

AB - Altered extracellular matrix (ECM) remodeling is an important part of the pathology of gastrointestinal (GI) disorders. In the intestine, type XVI collagen (col-16) plays a role in pathogenesis by affecting ECM architecture and induce cell invasion. Measuring col-16 in serum may therefore have biomarker potential in GI disorders such as colorectal cancer (CRC) and ulcerative colitis (UC). The aim of this study was to determine whether col-16 can serve as a biomarker for altered ECM remodeling in patients with CRC and UC. A monoclonal antibody was raised against the C-terminal end of col-16 (PRO-C16), and a competitive enzyme-linked immunosorbent assay (ELISA) was developed and technically validated. Levels of PRO-C16 were measured in serum from patients with CRC (before (n = 50) and 3 months after (n = 23) tumor resections), UC (n = 39) and healthy controls (n = 50). The PRO-C16 ELISA was specific toward the C-terminal of col-16. PRO-C16 was significantly elevated both in serum from patients with CRC (P = 0.0026) and UC (P < 0.0001) compared to controls. No difference was detected in levels of PRO-C16 between patients with CRC at baseline and 3 months after tumor resections (P > 0.999). Levels of PRO-C16 identified patients with a GI disorder with a positive predictive value of 0.9 and an odds ratio of 12 (95%CI = 4.5-29.5, P < 0.0001). The newly developed assay detected significantly elevated levels of PRO-C16 in serum from patients with GI disorders compared to controls suggesting its potential as a biomarker in this setting. Future studies are needed to validate these findings.

KW - Biomarkers

KW - Collagen

KW - Colorectal cancer

KW - Extracellular matrix

KW - Ulcerative colitis

U2 - 10.1002/cam4.1692

DO - 10.1002/cam4.1692

M3 - Journal article

VL - 7

SP - 4619

EP - 4626

JO - Cancer Medicine

JF - Cancer Medicine

SN - 2045-7634

IS - 9

ER -