Ascites-derived CDCP1+ extracellular vesicles subcluster as a novel biomarker and therapeutic target for ovarian cancer

Abstract

IntroductionOvarian cancer (OVCA) is one of the most prevalent malignant tumors of the female reproductive system, and its diagnosis is typically accompanied by the production of ascites. Although liquid biopsy has been widely implemented recently, the diagnosis or prognosis of OVCA based on liquid biopsy remains the primary emphasis.MethodsIn this study, using proximity barcoding assay, a technique for analyzing the surface proteins on single extracellular vesicles (EVs). For validation, serum and ascites samples from patients with epithelial ovarian cancer (EOC) were collected, and their levels of CDCP1 was determined by enzyme-linked immunosorbent assay. Tissue chips were prepared to analyze the relationship between different expression levels of CDCP1 and the prognosis of ovarian cancer patients.ResultsWe discovered that the CUB domain-containing protein 1+ (CDCP1+) EVs subcluster was higher in the ascites of OVCA patients compared to benign ascites. At the same time, the level of CDCP1 was considerably elevated in the ascites of OVCA patients. The overall survival and disease-free survival of the group with high CDCP1 expression in EOC were significantly lower than those of the group with low expression. In addition, the receiver operating characteristic curve demonstrates that EVs-derived CDCP1 was a biomarker of early response in OVCA ascites.DiscussionOur findings identified a CDCP1+ EVs subcluster in the ascites of OVCA patients as a possible biomarker for EOC prevention.

Recent advances of liquid biopsy: Interdisciplinary strategies toward clinical decision‐making

“…176 EVs in ascites also demonstrated great performance in cancer diagnosis 181 and therapy monitoring. 182 Even though EVs from various body fluids can reflect multi-dimensional situation of diseases, it can be noticed most of novel strategies focused on the universalavailable and high-stable fluids for feasibility verification, due to several challenges caused by their heterogeneous physical and chemical characteristics. For example, the EV concentration of urine and saliva is easily affected by different physiological conditions, and the timing of sample collection largely affects the results of EV detection.…”

“…Extracellular vesicles isolated from cerebrospinal fluid can reflect the situation of diseases related to brain and central nervous system like aneurysmal subarachnoid hemorrhage 177 and cancer leptomeningeal metastasis 176 . EVs in ascites also demonstrated great performance in cancer diagnosis 181 and therapy monitoring 182 …”