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

Cancer Med. 2018 Sep;7(9):4619-4626. doi: 10.1002/cam4.1692. Epub 2018 Jul 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Sequence
  • Biomarkers / blood*
  • Case-Control Studies
  • Colitis, Ulcerative / blood*
  • Colitis, Ulcerative / drug therapy
  • Colitis, Ulcerative / etiology
  • Colitis, Ulcerative / pathology*
  • Collagen / blood*
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / etiology
  • Colorectal Neoplasms / pathology*
  • Colorectal Neoplasms / therapy
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Matrix
  • Female
  • Humans
  • Male
  • Middle Aged
  • Models, Biological
  • Peptides / blood
  • Peptides / chemistry
  • ROC Curve
  • Young Adult

Substances

  • Biomarkers
  • COL16A1 protein, human
  • Peptides
  • Collagen