Circ-0001068 is a novel biomarker for ovarian cancer and inducer of PD1 expression in T cells

Ovarian cancer is a primary gynecological malignancy with a global 5-year survival rate of 44%. The majority of patients present with advanced disease at initial diagnosis because of the lack of an effective early detection screening test. Circular RNAs (circRNAs) within exosomes in the circulatory system are effective diagnostic and therapeutic biomarkers for many diseases, especially tumors. In this study, we used microarrays to identify 6 circRNAs that were upregulated and 37 circRNAs that were downregulated in exosomes from ovarian cancer patients as compared to healthy volunteers. We validated the accumulation trends for the 6 upregulated circRNAs in the training set using qRT-PCR and found that circ-0001068 was significantly higher in the serum exosomes from the ovarian cancer patients as than healthy volunteers. Circ-0001068 was next evaluated further in a larger cohort. As with the training set, results from the larger cohort revealed that levels of circ-0001068 in the exosomes were significantly higher in ovarian cancer patients than healthy volunteers. Circ-0001068 was also delivered into T cells and induced PD1 expression by acting as a competing endogenous RNA (ceRNA) for miR-28-5p through the exosomes.