Exosomal miR-1290 is a potential biomarker of high-grade serous ovarian carcinoma and can discriminate patients from those with malignancies of other histological types

Masaki Kobayashi, Kenjiro Sawada, Koji Nakamura, Akihiko Yoshimura, Mayuko Miyamoto, Aasa Shimizu, Kyoso Ishida, Erika Nakatsuka, Michiko Kodama, Kae Hashimoto, Seiji Mabuchi, Tadashi Kimura

microRNAs (miRNAs) stably exist in circulating blood encapsulated in extracellular vesicles such as exosomes; therefore, serum miRNAs have the potential to serve as novel cancer biomarkers. New diagnostic markers to detect high grade serous ovarian cancer (HGSOC) are urgently needed. The aim of this study was to identify miRNAs specific to HGSOC and analyze whether serum miRNA can discriminate HGSOC patients from healthy controls or patients with ovarian malignancies of other histological types. Exosomes from ovarian cancer cell lines were collected and exosomal miRNAs extracted. miRNA microarray analysis revealed several elevated miRNAs specific to HGSOC. Among these, we focused on miR-1290. Sera from 70 ovarian cancer patients and 13 healthy controls were gathered and its expression levels detected by quantitative real-time polymerase chain reaction. In HGSOC patients, serum miR-1290 was significantly overexpressed compared to in healthy controls (3.52 fold; P = 0.03), unlike in patients with ovarian cancers of other histological types. The relative expression of miR-1290 was higher in advanced stages of HGSOC than in early stages (4.23 vs. 1.58; P = 0.23). Its expression significantly decreased after operation (5.87 to 1.17; P < 0.01), indicating that this miRNA reflects tumor burden. A receiver operating characteristic curve analysis showed that at the cut-off of 1.20, the sensitivity and specificity were 63% and 85% respectively for discriminating patients with HGSOC (area under the curve [AUC] = 0.71) from healthy controls, and at the cut-off of 1.55, the sensitivity and specificity were 47% and 85% respectively for discriminating patients with HGSOC (AUC = 0.76) from those with malignancies of other histological types. Serum miR-1290 is significantly elevated in patients with HGSOC and can be used to discriminate these patients from those with malignancies of other histological types; it is a new potential diagnostic biomarker for HGSOC.