An Assay Quantifying Pro-Peptides Of Type Xi Collagen (Pro-C11) In Serum Provides Novel Insight Into The Pathology Of Non-Small Cell Lung Cancer (Nsclc)

Background: The tumor microenvironment (TME) is characterized by an extensive number and activity of cancer-associated fibroblasts (CAFs). CAFs are the most abundant cell type in the TME of stroma-rich tumors and dictate patient outcome. One of the most specific CAF genes is COL11A1 which encodes the α1-chain of type XI collagen. Type XI collagen is synthesized as a pro-collagen and proteolytically cleaved by bone-morphogenetic protein 1 (BMP-1) to yield mature type XI collagen. Cleaved pro-peptides released to the circulation could serve as biomarkers of type XI collagen formation and provide novel insight into patients with cancer. We developed and evaluated an assay targeting the N-terminal pro-peptide of type XI collagen for quantifying this specific fragment in the circulation (serum) of patients with non-small cell lung cancer (NSCLC). Methods: A monoclonal antibody was raised against the C-terminal neo-epitope on the N-terminal pro-peptide of type XI collagen and employed in the development of a competitive ELISA (PRO-C11). PRO-C11 was measured in serum from 40 stage 3+4 NSCLC patients and compared to 32 age-matched healthy controls. PRO-C11 was correlated with demographic and clinical characteristics (age, BMI, smoking, metastasis, histological subtype). Results: The PRO-C11 assay is technically robust with specificity only for the BMP-1 generated type XI collagen pro-peptide neo-epitope. PRO-C11 was significantly elevated in NSCLC compared to age-matched healthy controls (p 0.05) was seen between PRO-C11 and age, BMI, smoking status, metastasis (y/n) and histological subtype (squamous cell carcinoma vs. adenocarcinoma). Conclusion: The present study validates a new serological assay quantifying the pro-peptide of type XI collagen. The biomarker has promising potential for NSCLC and warrants further investigations into stroma-rich cancers. Further studies are needed to evaluate the diagnostic/prognostic use of PRO-C11 in NSCLC. Citation Format: Nicholas Willumsen, Stephanie N. Kehlet, Tina M. Jensen, Neel I. Nissen, Morten A. Karsdal. An assay quantifying pro-peptides of type XI collagen (PRO-C11) in serum provides novel insight into the pathology of non-small cell lung cancer (NSCLC) [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 3149.