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

Lingnan Kong; Famei Xu; Yukuan Yao; Zhihui Gao; Peng Tian; Shichao Zhuang; Di Wu; Tangyue Li; Yanling Cai; Jing Li

doi:10.3389/fonc.2023.1142755

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

Front Oncol. 2023 Jul 3:13:1142755. doi: 10.3389/fonc.2023.1142755. eCollection 2023.

Authors

Lingnan Kong^{1

2}, Famei Xu², Yukuan Yao^{1

2}, Zhihui Gao², Peng Tian³, Shichao Zhuang⁴, Di Wu^{5

6}, Tangyue Li², Yanling Cai⁷, Jing Li²

Affiliations

¹ Affiliated Hospital of Weifang Medical University, School of Clinical Medicine, Weifang Medical University, Weifang, China.
² Department of Pathology, Zibo Central Hospital, Zibo, China.
³ Department of Ultrasonic, Zibo Central Hospital, Zibo, China.
⁴ Department of Gynecology, Zibo Central Hospital, Zibo, China.
⁵ Department of R&D, Shenzhen SecreTech Co., Ltd., Shenzhen, China.
⁶ Department of R&D, Vesicode AB, Solna, Sweden.
⁷ Guangdong Provincial Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.

Abstract

Introduction: Ovarian 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.

Methods: In 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.

Results: We 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.

Discussion: Our findings identified a CDCP1+ EVs subcluster in the ascites of OVCA patients as a possible biomarker for EOC prevention.

Keywords: CDCP1; ascites; diagnose; extracellular vesicles; ovarian cancer.

Grants and funding

This research was funded by Natural Science Foundation of Shandong Province, China, Grant Number ZR2022MH053; Zibo Key Research and Development Program, Grant Number 2019gy010006; Zibo Science and Academic Development Program, Grant Number 2018kj010078; Open Project of Zibo Gene Detection Technology Key Laboratory, Grant Number 2021WL01KF01.