Type XIX collagen quantified in serum targeting the anti-tumorigenic NC1 domain is elevated in early and late stage lung carcinoma patients and COPD

Abstract

Introduction: Twenty-eight collagens exists, for which few tools are available. The FACIT collagens are emerging proving equally important to the fibrillar collagens, including type XIX collagen, which is located in the basement membrane and has been linked to breast cancer progression. The NC1 domain of type XIX collagen may have anti-tumorigenic signalling properties.

Methods: A specific monoclonal antibody was raised towards the C-terminus of type XIX collagen, and a technical robust competitive ELISA (PRO-C19) was developed. PRO-C19 was assessed in the serum of: 1) Patients with a range of cancer types including NSCLC n=11; SCLC n=7; breast cancer n=12; ovarian cancer n=8; colon cancer n=7; gastric cancer n=9; pancreatic cancer n=2; prostate cancer n=13 and melanoma cancer n=6. 2) Patients with NSCLC stages III and IV versus healthy controls n=40. 3) Patients with early stage NSCLC, including stages I-IV n=34. 4) 10 COPD, 20 NSCLC vs 20 controls.

Results: PRO-C19 was elevated in patients with NSCLC (p<0.0001), SCLC (p=0.0081), breast cancer (p=0.0005) and ovarian cancer (p<0.0001) compared to healthy controls. Furthermore, it was shown that PRO-C19 was able to significantly identify patients with NSCLC stages III and IV versus controls (AUROC=0.98); stage I and II versus controls (AUROC=0.76); and COPD and NSCLC vs controls (AUROC=0.77 and 0.98, respectively)

Conclusion: A novel marker for type XIX collagen was associated to various cancer types in particular the staging of NSCLS. This suggests that type XIX collagen may be of particular relevance and pathological meaning in the tumor microenvironment