Exosomal MicroRNA as Biomarkers for Diagnosing or Monitoring the Progression of Ovarian Clear Cell Carcinoma: A Pilot Study

Abstract

Ovarian cancer is the most common cause of gynecological malignancy-related mortality since early-stage disease is difficult to diagnose. Advanced clear cell carcinoma of the ovary (CCCO) has dismal prognosis, and its incidence has been increasing in Japan, emphasizing the need for highly sensitive diagnostic and prognostic CCCO biomarkers. Exosomal microRNAs (miRNAs) secreted by tumor cells are known to play a role in carcinogenesis; however, their involvement in ovarian cancer is unclear. In this study, we performed expression profiling of miRNAs from exosomes released by five cell lines representing different histological types of ovarian cancer. Exosomes isolated from culture media of cancer and normal cells were compared for miRNA composition using human miRNA microarray. We detected 143 exosomal miRNAs, whose expression was ≥1.5-fold higher in ovarian cancer cells than in the control. Among them, 28 miRNAs were upregulated in cells of all histological ovarian cancer types compared to control, and three were upregulated in CCCO cells compared to other types. Functional analyses indicated that miR-21 overexpressed in CCCO cells targeted tumor suppressor genes PTEN, TPM1, PDCD4, and MASP1. The identified miRNAs could represent novel candidate biomarkers to diagnose or monitor progression of ovarian cancer, particularly CCCO.

Adipose-derived exosomal miR-421 targets CBX7 and promotes metastatic potential in ovarian cancer cells

“…Although free miRNAs can be detected in the circulation, the protective effect of exosomal membranes contribute to its stability (68). Indeed, exosomal miRNAs have been proposed as biomarkers for OC (80, 81). And, adipocyte derived exosomes have been successfully detected in blood (65).…”

Cancer-Specific miRNAs Extracted from Tissue-Exudative Extracellular Vesicles in Ovarian Clear Cell Carcinoma

“…Several studies have reported the presence of cancer-specific miRNAs in OCC. In these studies, miRNAs were extracted directly from cell lines and tissues, or from EVs secreted by cell lines [ 25 , 26 , 27 ]. Wyman et al compared miRNAs extracted from ovarian serous, endometrial, and clear cell carcinoma tissues with those extracted from normal ovarian surface epithelial cells.…”

“…Horie et al extracted and profiled miRNAs from EVs from four histological types of ovarian cancer cell lines (serous, endometrial, mucinous, and clear cells). They reported that three miRNAs (miR−21−5p, miR29a−3p and miR−30d−5p) were highly expressed in OCC [ 27 ]. In the current study, the expression levels of miR−200c−3p, miR−200a−3p, miR200b−3p, miR−200b−5p, miR−200a−5p, miR−30a−5p, miR−30b−5p, and miR−21−5p in Te-EVs extracted from OCC tissues were significantly higher than those in normal ovaries.…”

Unlocking Exosome-Based Theragnostic Signatures: Deciphering Secrets of Ovarian Cancer Metastasis

“…Exosomes are a promising source of cancer biomarkers. − In OC, it supports early detection of it. Exosome association in OC biomarker research is explained in Figure .…”