Upregulated expression of serum exosomal miR-375 and miR-1307 enhance the diagnostic power of CA125 for ovarian cancer

Abstract

BackgroundOvarian cancer (OC) is associated with high mortality in gynecological oncology; this is mainly due to the low diagnosis rate. Exosomal miRNA has demonstrated potential as a tumor biomarker. We aimed to explore the diagnostic potential of serum exosomal miR-1307 and miR-375 for OC.MethodsThe first six candidate miRNAs were selected from the previous literature. The relative quantification of qRT-PCR was used to screen for the stability of exosomal miRNAs, followed by validation of the cohort. ROC analysis was employed to analyze the specificity and sensitivity of exosomal miRNA.ResultsMiR-1307 and miR-375 were confirmed stably existing in serum exosomes of OC. Moreover, miR-1307 and miR-375 were both significantly up-regulated in serum exosomes of OC compared to ovarian benign and healthy groups. The overexpressed miRNAs showed independent diagnostic power and enhanced the diagnostic accuracy of traditional biomarkers when combined with CA-125 and HE4. MiR-1307 was associated with tumor staging, and miR-375 was associated with lymph node metastasis of OC.ConclusionOur results suggest that serum exosomal miR-1307 and miR-375 could serve as potential tumor biomarkers to improve diagnostic efficiency for OC.

Serum exosomal microRNA-34a as a potential biomarker in epithelial ovarian cancer

“…In addition, several previous studies have shown that stable circulating miRNAs play an increasingly important role in the diagnosis of OC [9][10][11][12][13][14][15]. However, to our knowledge, few reports have described miRNA levels in exosomes isolated from the plasma of OC patients [16][17][18][19]. Tissue miRNAs present poor stability, but exosomal miRNAs in serum are thought to be more stable [28].…”

“…As we demonstrated, transmission electron microscopy revealed that the clusters isolated from serum were round or oval membrane vesicles largely between 30 and 100 nm in size and were homogeneous in appearance, suggesting that these vesicles were exosomes. Previous studies have also shown the significance of detecting exosomes using immunoblotting against CD63 and electron microscopy [16,21,32].…”

“…Exosomes derived from cancer contain tumor cellspecific miRNA, and hence they may be useful as potential biomarkers of disease progression. However, few reports have focused on serum exosomal miRNA [16][17][18][19], and thus this study may include some unique findings or interpretations. Interestingly, the analysis of the relative expression of serum exosomal miRNA in our study revealed that early-stage OC patients had significantly higher levels of exosomal miR-34a than advanced-stage patients.…”

Highly expressed miR-375 is not an intracellular oncogene in Merkel cell polyomavirus-associated Merkel cell carcinoma

“…Taking these results together with our previous observations that miR-375 is present in MCC cell line conditioned medium, in sera of preclinical xenotransplantation animal models and in sera of MCC patients [10] suggest, miR-375 may rather serve intercellular than intracellular signaling in MCC. Indeed, miR-375 was recently characterized as an exosomal shuttle miRNA [24,25].…”

Circulating non-coding RNAs in recurrent and metastatic ovarian cancer

“…Apart from miR-193a-5p, the deregulated plasma levels of which were also reported in recurrent platinum resistant OC patients [146] , the improvement of the diagnostic power of CA125 and HE4 for OC was also shown to be mediated by serum exosomal miR-375 and miR-1307. Su et al [151] detected that both miR-375 and miR-1307 were significantly up-regulated in serum exosomes of OC compared with ovarian benign and healthy groups. Notably, exosomal miR-375 correlated with lymph node metastasis of OC [151] .…”