Integrated analysis of ascites and plasma extracellular vesicles identifies a miRNA-based diagnostic signature in ovarian cancer. (28th August 2022)

• Record Type: Journal Article
• Authors: Wang, Wenyu; Jo, HyunA; Park, Sangick; Kim, Heeyeon; Kim, Se Ik; Han, Youngjin; Lee, Juwon; Seol, Aeran; Kim, Junhwan; Lee, Maria; Lee, Cheol; Dhanasekaran, Danny N.; Ahn, Taejin; Song, Yong Sang
• Is Part Of: Cancer letters. Volume 542(2022)
• Publication Date: 2022-08-28
• Subjects: Liquid biopsy -- Invasion -- Migration -- miR-1246 -- miR-1290; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2022.215735
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Ovarian cancer is mostly diagnosed at advantaged stages due to the lack of early diagnostic biomarkers. The common metastasis pattern is characterized by peritoneal dissemination with a formation of malignant ascites. Extracellular vesicles (EVs) are emerging as promising clinical biomarkers in liquid biopsy. Here, we aimed to investigate robust liquid biopsy-based EV miRNA biomarkers for ovarian cancer diagnosis and metastasis regulation. EVs were isolated from malignant ascites and plasma of ovarian cancer patients as well as the benign control counterparts of patients with benign gynecologic diseases. EV small RNA sequencing identified a panel of eight miRNAs (miR-1246, miR-1290, miR-483, miR-429, miR-34b-3p, miR-34c-5p, miR-145–5p, miR-449a) based on dysregulated miRNAs overlapped in the ascites and plasma subset. The ovarian cancer EV miRNA (OCEM) signature developed based on these eight miRNAs demonstrated high diagnostic accuracy in our in-house dataset and multiple public datasets across diverse clinical samples (blood, tissue and urine). In addition, malignant ascites-derived EVs could significantly facilitate the aggressive property of ovarian cancer cells and boost the growth of ascites-derived organoids. Notably, miR-1246 and miR-1290 shuttled in malignant ascites-derived EVs were identified to promote the invasion and migration of ovarian cancer cells through regulating a common target RORα. Highlights: The ovarian cancer EV miRNA (OCEM) diagnostic signature was developed based on the integrated analysis of ascites and plasma. OCEM signature revealed a high diagnostic ability in in-house and public datasets. Malignant ascites-derived EVs facilitated the invasion and migration of ovarian cancer cells. miR-1246 and miR-1290 contributed to the pro-aggressive effect of malignant ascites-derived EVs by targeting RORα.