Role of EpCAM-Positive Exosomes in Ovarian Cancer: MiRNA Signatures of Chemoresistance and Disease Progression

Ovarian cancer (OC) is a complex disease with challenges such as delayed diagnosis and development of chemoresistance. Exosomes play a crucial role in intercellular communication within the tumor microenvironment and have been reported to transmit drug-resistant traits and promote proliferation and metastasis. We aimed to investigate the role of exosomal miRNAs in OC, focusing on their involvement in chemoresistance, immune evasion, and metastasis.

We investigated the expression levels of miR-182, miR-9, miR-130a, miR-20a, and miR-23b, which are implicated in chemoresistance, immune evasion, and metastasis in OC. We used real-time PCR to assess the expression of these miRNAs in different exosomal and non-exosomal fractions isolated from the serum of 20 chemo naive, 20 chemotreated, and 20 healthy women.

Our results revealed that ovarian tumors release higher levels of EpCAM-positive exosomes, which carry specific miRNAs that reflect the tumor's influence on the exosomal cargo. Elevated levels of miR-182, and miR-9 were found in EpCAM-positive exosomes from OC patients, with miR-182 being associated with disease relapse and the FIGO stage. In addition, miR-20a was found to be elevated in exosomes from chemotherapy-treated OC patients, indicating chemotherapy's impact on the exosomal miRNA profile. Notably, the miRNA expression in EpCAM-negative exosomes remained unchanged, highlighting the selective loading of miRNAs in EpCAM-positive exosomes.

Overall, the study highlights a probable mechanism for miRNA packaging and release in OC through EpCAM-positive exosomes, offering potential biomarkers for monitoring disease progression and relapse.