Circulating Exosomal miRNAs as Biomarkers in Epithelial Ovarian Cancer

Abstract

Failure to detect early-stage epithelial ovarian cancer (EOC) is a major contributing factor to its low survival rate. Increasing evidence suggests that different subtypes of EOC may behave as distinct diseases due to their different cells of origins, histology and treatment responses. Therefore, the identification of EOC subtype-specific biomarkers that can early detect the disease should be clinically beneficial. Exosomes are extracellular vesicles secreted by different types of cells and carry biological molecules, which play important roles in cell-cell communication and regulation of various biological processes. Multiple studies have proposed that exosomal miRNAs present in the circulation are good biomarkers for non-invasive early detection of cancer. In this review, the potential use of exosomal miRNAs as early detection biomarkers for EOCs and their accuracy are discussed. We also review the differential expression of circulating exosomal miRNAs and cell-free miRNAs between different biofluid sources, i.e., plasma and serum, and touch on the issue of endogenous reference miRNA selection. Additionally, the current clinical trials using miRNAs for detecting EOCs are summarized. In conclusion, circulating exosomal miRNAs as the non-invasive biomarkers have a high potential for early detection of EOC and its subtypes, and are likely to be clinically important in the future.

The current trend of exosome in epithelial ovarian cancer studies: A bibliometric review

“…Only articles published in English were included. After the exclusion of duplicate, irrelevant journal articles and non-journal articles, 39 articles on exosome and EOC were selected for bibliometric analysis; 36 of which were original articles ( Zhang et al, 2016a ; Meng et al, 2016b ; Zhang et al, 2016b ; Labani-Motlagh et al, 2016 ; Ying et al, 2016 ; Chen et al, 2017 ; Hu et al, 2017 ; Li et al, 2017 ; Wu et al, 2017 ; Chen et al, 2018 ; Qiu et al, 2018 ; Zhang et al, 2018 ; Zhou et al, 2018 ; Zhang et al, 2019a ; Keserű et al, 2019 ; Tang et al, 2019 ; Zhu et al, 2019 ; Cheng et al, 2020 ; Li et al, 2020 ; Lu et al, 2020 ; Luo and Gui, 2020 ; Maeda et al, 2020 ; Masoumi-Dehghi et al, 2020 ; Alharbi et al, 2021 ; Xiong et al, 2021a ; Cai et al, 2021 ; Gao et al, 2021 ; Li et al, 2021 ; Liu et al, 2021 ; Ma et al, 2021 ; Zhu et al, 2022a ; Chen et al, 2022 ; Jeon et al, 2022 ; Lai et al, 2022 ; Yang et al, 2022 ), and the rest of them were review articles ( Li and Wang, 2017 ; Lucidi et al, 2020 ; Shiao et al, 2021 ). The first English article is “Characterization of exosomes derived from ovarian cancer cells and normal ovarian epithelial cells by nanoparticle tracking analysis” in 2015 ( Zhang et al, 2016a ).…”

Circulating Biomarkers for Cancer Detection: Could Salivary microRNAs Be an Opportunity for Ovarian Cancer Diagnostics?

“…In plasma samples, coagulation is prevented by adding EDTA and, through centrifugation at high speeds for a long time, platelet-depleted plasma can be easily obtained. In turn, in serum samples, clot-activation causes the release of different biological molecules (also miRNAs) from platelets [ 105 ]. Even if, for the above reason, plasma should be considered the sample of choice to detect circulating CF-miRNAs, hemolysis can in both cases affect the accuracy of serum or plasma-based tests.…”

“…However, endogenous controls can also be used for circulating miRNAs, for example, small nuclear and nucleolar RNA such as U6, RNU44, RNU43, and RNU48. Several authors proposed other internal controls that were more stable in the biofluids of their interest, making comparisons across different articles even more difficult [ 105 ].…”

“…In addition, most of the published studies on exosomal miRNAs do not use high-throughput discovery approaches as a first step. Instead, they mostly select candidate exosomal miRNAs from the literature and then proceed with validation or functional assays [ 105 ].…”

Four differentially expressed exosomal miRNAs as prognostic biomarkers and therapy targets in endometrial cancer: Bioinformatic analysis

“…Because of the heterogeneity of cancer cells, exosomal miRNAs from host cancer cells can activate the receptors or change miRNA or RNA expression in the neighboring cancer cells to alter their biological phenotypes. [12] Numerous publications present various exosomal miRNAs as potential biomarkers of breast cancer, [20] lung cancer, [21][22][23][24] gastric cancer, [25][26][27][28] colorectal cancer, [29][30][31][32] EC, [33] epithelial ovarian cancer, [34] and other cancers. [35][36][37][38][39][40][41][42][43][44][45] Here, as reported by Srivastava A etc, exosomes with a unique miRNA signature can be isolated from the urine of symptomatic women who are diagnosed with EC.…”