Abstract 3953: Serum type XIX collagen is significantly elevated in non-small cell lung cancer and is a biomarker with clinical potential

Abstract

Abstract Introduction: Type XIX collagen is a poorly characterized collagen associated with the basement membrane zone along with type XVIII and XV collagen. Type XIX collagen has shown altered regulation during tumor progression of melanoma and breast cancer. In this study, we developed and validated an ELISA targeting the natural C-terminus of type XIX collagen and quantified it in serum of cancer patients, demonstrating the biomarker potential of type XIX collagen. Methods: A monoclonal antibody was raised against the C-terminus of type XIX collagen and utilized in a competitive ELISA named PRO-C19. PRO-C19 was quantified in serum from patients with breast (n=12), colon (n=7), gastric (n=9), melanoma (n=6), non-small cell lung cancer (NSCLC) (n=11), small cell lung cancer (SCLC) (n=7), ovarian (n=8), pancreas (n=2), prostate cancer (n=13) and healthy controls (n=38). PRO-C19 was further assessed in another cohort comprising stage III (n=20) and stage IV (n=20) NSCLC patients and healthy controls (n=24). Lastly, PRO-C19 was assessed in the conditioned media of a cell model mimicking the fibroblast activation found in fibrotic lung diseases using lung fibroblasts stimulated with TGF-β. Results: The PRO-C19 assay was technically robust and specific for the C-terminus of type XIX collagen. PRO-C19 was significantly elevated in serum from breast (p=0.0201), NSCLC (p<0.0001) and ovarian cancer patients (p=0.0108) compared to healthy controls. PRO-C19 was also elevated in colon, pancreatic and SCLC cancers, although this was not statistically significant. The separation between NSCLC and healthy controls was excellent as demonstrated by an AUROC of 0.995 (p<0.0001). Consequently, PRO-C19 was also assessed in a separate cohort of NSCLC patients. Here PRO-C19 was also significantly elevated in NSCLC patients compared to healthy controls (p<0.0001) and the AUROC was 0.980 (p<0.0001). Lastly, because PRO-C19 performed well in lung cancer, we assessed it in a lung fibrosis cell model. PRO-C19 was found in the conditioned media of the lung fibroblasts, but levels were independent of TGF-β stimulation. Conclusion: This study demonstrates that type XIX collagen is elevated in several types of cancer and proved excellent at separating NSCLC and healthy controls. The elevated levels seen in NSCLC patients do not seem to be induced by lung fibrosis. This all provide novel clues to the function of type XIX collagen - an otherwise poorly characterized collagen. Further investigations are ongoing to explore diagnostic or prognostic uses of PRO-C19 and the function of type XIX collagen. Citation Format: Jeppe Thorlacius-Ussing, Samuel Daniels, Morten Karsdal, Nicholas Willumsen. Serum type XIX collagen is significantly elevated in non-small cell lung cancer and is a biomarker with clinical potential [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3953.