Exosomal microRNA Signatures in the Diagnosis and Prognosis of Ovarian Cancer

摘要

Our original goal was to correlate exosomal miRNA profiles within circulating tumor-derived exosomes with cancer diagnosis, characterization of circulating tumor-derived vesicles and development of methodology for their specific isolation were essential for specific analyses of tumor-derived exosomal cargoes. Our discovery of exosomal microRNA in cancer patients focused on miRNAs, previously demonstrated in tumor biopsies or ovarian tumor cells. We have observed that while some miRNAs that are up-regulated with the tumor or also up-regulated in their exosomes, some tumor-up-regulated miRNAs are not up- regulated within exosomes. Further, certain miRNAs down-regulated within the tumor are up-regulated in exosomes. We demonstrate that miRNA signatures derived from ovarian tumor exosomes exhibit some miRNAs that are undetectable within the tumor. These findings demonstrate the highly selective nature of miRNA packaging. Although the exosomal miRNA signatures for ovarian cancer patients appear to be similar regardless of stage, significant differences among early (Stage I and II) and late stage (Stage III) ovarian cancer were demonstrated: increase expression level and elevated expression of three specific miRNAs within exosomes. Exosomes from ovarian cancer patients were demonstrated to possess elevated levels of RNA, including the presence of specific long-noncoding RNA.