Serum Type XIX Collagen is Significantly Elevated in Non-Small Cell Lung Cancer: A Preliminary Study on Biomarker Potential

• Main Authors: Jeppe Thorlacius-Ussing, Tina Manon-Jensen, Shu Sun, Diana J. Leeming, Jannie M. Sand, Morten Karsdal, Nicholas Willumsen
• Format: Article
• Language: English
• Published: MDPI AG 2020-06-01
• Series: Cancers
• Subjects: Collagen XIX; ECM; biomarker; serum; cancer; NSCLC
• Online Access: https://www.mdpi.com/2072-6694/12/6/1510

Type XIX collagen is a poorly characterized collagen associated with the basement membrane. It is abnormally regulated during breast cancer progression and the NC1 (XIX) domain has anti-tumorigenic signaling properties. However, little is known about the biomarker potential of collagen XIX in cancer. In this study, we describe a competitive ELISA, named PRO-C19, targeting the C-terminus of collagen XIX using a monoclonal antibody. PRO-C19 was measured in serum of patients with a range of cancer types and was elevated in non-small cell lung cancer (NSCLC) (<i>p</i> < 0.0001), small cell lung cancer (<i>p</i> = 0.0081), breast (<i>p</i> = 0.0005) and ovarian cancer (<i>p</i> < 0.0001) compared to healthy controls. In a separate NSCLC cohort, PRO-C19 was elevated compared to controls when evaluating adenocarcinoma (AD) (<i>p</i> = 0.0003) and squamous cell carcinoma (SCC) (<i>p</i> < 0.0001) patients but was not elevated in chronic obstructive pulmonary disease patients. SCC also had higher PRO-C19 levels than AD (<i>p</i> = 0.0457). PRO-C19 could discriminate between NSCLC and healthy controls (AUROC:0.749 and 0.826 for AD and SCC, respectively) and maintained discriminatory performance in patients of tumor stages I+II (AUROC:0.733 and 0.818 for AD and SCC, respectively). Lastly, we confirmed the elevated type XIX collagen levels using gene expression data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) initiatives. In conclusion, type XIX collagen is released into circulation and is significantly elevated in the serum of cancer patients and PRO-C19 shows promise as a cancer biomarker.