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.

Prognostic value of blood-based fibrosis biomarkers in patients with metastatic colorectal cancer receiving chemotherapy and bevacizumab

“…Overall, studies report contradicting results showing that desmoplasia is a complex and heterogeneous reaction 6 , 20 , 49 – 52 . Nonetheless, we and others have shown that collagen fragments, including PRO-C3 and PRO-C6, are increased in serum from CRC patients, and that the levels of these fragments increase in later stages of disease 43 , 44 , 47 , 53 – 55 . In this study, we show that collagen fragments are expressed in same levels as reported before in CRC 38 , 44 .…”

Extracellular Matrix Biomarkers in Colorectal Cancer

“…There are increased levels of the C-terminal end of type XVI collagen in the serum of CRC patients [54]. In addition, type XVI collagen is upregulated by transforming growth factor-β (TGF-β) [55]; high levels of TGF-β are associated with metastasis and a poor outcome in CRC patients [55,56].…”

Modulation of the extracellular matrix by Streptococcus gallolyticus subsp. gallolyticus and importance in cell proliferation

“…Altered ECM composition, structure and mechanical property are common features in tumor tissues and contribute to tumor progression [18][19][20][21][22][23]. In the case of CRC, multiple studies have found that various types of collagens are upregulated in tumors compared to matched normal tissues [24][25][26][27][28][29][30][31]. Whether gut microbes can provide exogenous signals to modulate ECM expression and dynamics was unknown.…”