Clinical relevance of circulating cell-free microRNAs in ovarian cancer

Ovarian cancer is the leading cause of death among gynecologic malignancies. Since ovarian cancer develops asymptomatically, it is often diagnosed at an advanced and incurable stage. Despite many years of research, there is still a lack of reliable diagnostic markers and methods for early detection and screening.

Recently, it was discovered that cell-free microRNAs (miRNAs) circulate in the body fluids of healthy and diseased patients, suggesting that they may serve as a novel diagnostic marker. Despite the high levels of ribonucleases in many types of body fluids, most of the circulating miRNAs are packaged in microvesicles, exosomes, or apoptotic bodies, are binding to RNA-binding protein such as argonaute 2 or lipoprotein complexes, and are thus highly stable. Cell-free miRNA signatures are known to be parallel to those from the originating tumor cells, indicating that circulating miRNA profiles accurately reflect the tumor profiles. Since it is well established that the dysregulation of miRNAs is involved in the tumorigenesis of ovarian cancer, cell-free miRNAs circulating in body fluids such as serum, plasma, whole blood, and urine may reflect not only the existence of ovarian cancer but also tumor histology, stage, and prognoses of the patients.

Several groups have successfully demonstrated that serum or plasma miRNAs are able to discriminate patients with ovarian cancer patients from healthy controls, suggesting that the addition of these miRNAs to current testing regimens may improve diagnosis accuracies for ovarian cancer. Furthermore, recent studies have revealed that changes in levels of cell-free circulating miRNAs are associated with the condition of cancer patients. Discrepancies between the results across studies due to the lack of an established endogenous miRNA control to normalize for circulating miRNA levels, as well as differing extraction and quantification methods, are the pitfalls to be resolved before clinical application. There is still a long way, however, before this can be achieved, and further evidence would make it possible to apply circulating cell-free miRNAs not only as biomarkers but also as potential therapeutic targets for ovarian cancer in the future.

miRNAs in various human body fluids

exosome rna

miRNAs can be detected in various human body fluids. Circulating miRNAs reported as potential non-invasive diagnostic markers for many types of cancers are shown. miRNAs which were reported to be upregulated in cancer patients compared to controls (healthy or benign) are shown in red, and those downregulated in cancer patients are shown in blue. In [39], miR-21 and miR-1225-5p were overexpressed in ascites from serosa-invasive gastric cancer patients compared with non-invasive gastric cancer patients. In breast milk, 3 most abundant miRNAs are listed in the figure. PCNSL: primary central nervous system lymphoma; NSCLC: non-small cell lung cancer.

Nakamura K, Sawada K, Yoshimura A, Kinose Y, Nakatsuka E, Kimura T. (2016) Clinical relevance of circulating cell-free microRNAs in ovarian cancer. Mol Cancer 15(1):48. [article]

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