Diagnostic and prognostic relevance of circulating exosomal miR-373, miR-200a, miR-200b and miR-200c in patients with epithelial ovarian cancer

Abstract

Exosomes are membrane vesicles that mediate intercellular communication by transporting their molecular cargo from cell to cell. We investigated whether serum levels of exosomal miR-373, miR-200a, miR-200b and miR-200c and circulating exosomes have diagnostic and prognostic relevance in a cohort of 163 epithelial ovarian cancer (EOC) patients using TaqMan MicroRNA assays and ELISA. The serum concentrations of exosomal miR-373 (p = 0.0001), miR-200a (p = 0.0001), miR-200b (p = 0.0001) and miR-200c (p = 0.028) were significantly higher in EOC patients than healthy women. The levels of miR-200a (p = 0.0001), miR-200b (p = 0.0001) and miR-200c (p = 0.019) could distinguish between malignant and benign ovarian tumors. While the levels of miR-373 and miR-200a were increased in all FIGO/lymph node stages (p = 0.0001), the levels of miR-200b and miR-200c were higher in patients with FIGO stage III–IV (p = 0.0001, p = 0.008, respectively) including lymph node metastasis (p = 0.0001, p = 0.004, respectively) than FIGO stages I–II. The increased levels of miR-200b and miR-200c were also associated with CA125 values (p = 0.0001, p = 0.0001, respectively) and a shorter overall survival (p = 0.007, p = 0.017, respectively). The levels of exosomes were excessively elevated in EOC patients (p = 0.0001). In all three cohorts, they were positively associated with the serum levels of exosomal miR-373 (p = 0.004), miR-200a (p = 0.0001), miR-200b (p = 0.0001) and miR-200c (p = 0.008). In conclusion, the increased levels of exosomal miR-200b and miR-200c mainly observed in advanced EOC suggest that these microRNAs may be involved in tumor progression. The high concentrations of exosomes in EOC patients imply an excessive, active exosomal secretion in EOC.

Diagnostic relevance of circulating cell-free and exosomal microRNAs and long non-coding RNAs in blood of cancer patients

“…Moreover, we observed a cancer-specific upregulation of exosomal miR-200a, miR-200b and miR-200c and their ability to distinguish between malignant and benign ovarian tumors. Exosomal miR-200b and miR-200c were associated with lymph node-positive status, advanced tumor (FIGO) stages, values of the tumor marker CA125 and poor overall survival in EOC patients [78].…”

The role of extracellular vesicle microRNAs in cancer biology

“…Several studies have shown that exosomal miRNAs can be detected in a variety of body fluids, from blood to breast milk, and that their levels are correlated with patient status [4,5,[60][61][62][63][64][65][66][67][68][69][70][71][72][73] (Table 1). On January 21, 2016, cancer diagnosis using exosomes from blood became commercially available in the US (http://www.exosomedx.com) [6].…”

“…Several studies have reported that specific exosomal miRNAs are associated with the condition of cancer patients [5,67,73]. In epithelial ovarian cancer (EOC), serum exosome levels are elevated, and high levels of exosomal miR-200b and miR-200c are observed mainly in patients with advanced EOC [5].…”

“…Therefore, manipulation of miRNA expression represents a promising approach to cancer therapy. Several recent studies report that miRNAs are secreted through exosomes, and that the levels of circulating miRNAs packaged in exosomes differ between cancer patients and healthy donors [4][5][6]. More importantly, the contents and amount of secreted microRNA (se-miRNAs) are associated with disease stage and regulation of the malignant phenotype [7][8][9].…”

Keringő mikroRNS-ek az endokrin daganatok diagnosztikájában

“…Egyes endokrin daganatok keringő mikroRNS-einek mintázatának leírása fokozatosan gyarapodik (l. PTC, ACC, csírasejtes heretumor, ovariumcarcinoma), de még lemaradásban vannak más területek vizsgálatához (például gastrointestinalis daganatokhoz) képest. Ezt természetesen megnehezítik azok a ténye-zők, mint például a pheochromocytoma rendkívül szerteágazó etiológiája [48][49][50], vagy a mellékvesekéreg-adenomák különböző hormontermelésének megléte vagy hiánya. Ugyanitt lehetne említeni az agyalapi mirigy daganatait is.…”