Abstract 1340: Type XVII collagen biology is central in the fibro-immune axis of tumor fibrosis: serological assessment of type XVII collagen

Abstract

Abstract Background: Collagens are the main components of the desmoplastic reaction of the tumors stroma, resulting in tumors fibrosis. Immuno-oncology (IO) is a central part of treating and understanding solid tumor patients. Alterations in the extracellular matrix (ECM) are known to contribute to tumor progression and metastasis. Collagen XVII (BP180) is a type II transmembrane protein that plays a unique role in the ECM with both fibrotic and auto-antigenicity properties, both central aspects in tumor biology. Aberrant expression and ectodomain shedding of collagen XVII have been associated with tumor invasiveness and metastasis in multiple tumor types such as colorectal, breast, pancreatic or ovarian carcinoma. In this study, we developed an ELISA targeting the collagen XVII ectodomain and investigate the non-invasive biomarker potential across different tumor types. Methods: An ELISA (PRO-C17) was developed based on a monoclonal antibody raised against the NC16a ectodomain of collagen XVII. The ELISA was optimized and validated for accuracy and precision in human serum. PRO-C17 biomarker levels were measured in 214 patients with different kinds of cancer including bladder (n = 19), breast (n = 19), colorectal (n = 20), head and neck (n = 20), kidney (n = 20), lung (n = 17), melanoma (n = 20), ovarian (n = 20), pancreatic (n = 20), prostate (n = 19), and stomach cancer (n = 20). PRO-C17 levels in cancer patients were compared to healthy individuals (n = 23) by Kruskal Wallis H test and Dunn’s multiple comparisons test. The diagnostic power of the biomarker was assessed by the area under the curve (AUC) of the receiver-operating characteristics (ROC). Results: PRO-C17 was technically robust and specific for the collagen XVII ectodomain, as showed by western blot of supernatant from A431 cells expressing and shedding collagen XVII. PRO-C17 was significantly increased in serum from patients with bladder (p = 0.04, AUC = 0.752), breast (p = 0.01, AUC = 0.777), colorectal (p < 0.0001, AUC = 0.904), head and neck (p = 0.002, AUC = 0.828), kidney (p = 0.01, AUC = 0.789), and ovarian cancer (p = 0.004, AUC = 0.76) compared to healthy individuals. No difference was observed in patients with lung (p = 0.23, AUC = 0.739), melanoma (p = 0.06, AUC = 0.737), pancreatic (p > 0.9, AUC = 0.722), prostate (p = 0.29, AUC = 0.727), and stomach cancer (p > 0.9, AUC = 0.690). Conclusion: Type XVII collagen was important across solid tumor types. When quantified in serum, type XVII collagen levels were significantly elevated in serum from patients with specific types of cancer only, which may indicate the disruption of the adhesion of epithelial cells to the basement membrane during tumor invasion. These findings suggest PRO-C17 as a promising non-invasive biomarker that can aid in understanding tumor heterogeneity as well as elaborate on the role of collagen XVII in the balance of fibrosis and auto-autoimmunity of tumor progression. Citation Format: Marina Crespo-Bravo, Rasmus S. Pedersen, Jeppe Thorlacius-Ussing, Nicholas Willumsen, Morten A. Karsdal. Type XVII collagen biology is central in the fibro-immune axis of tumor fibrosis: serological assessment of type XVII collagen [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1340.