MiRNome alterations drive the malignant transformation of endometriosis into endometriosis-correlated ovarian cancer

Endometriosis (EMS) is a chronic gynecological condition affecting 6-10% of reproductive-age women. These lesions, albeit of benign nature, present cancer-like features, and may progress to epithelial ovarian cancer (EOC) through a multistep process. The coexistence of EMS and EOC in the presence of transitional lesions (TL) - i.e. atypical EMS/borderline lesions - is termed as endometriosis-correlated ovarian cancer (ECOC). Given the regulatory role of miRNAs in gene expression and biological pathways, we aimed to identify miRNAs that may drive or modulate the malignant transformation of ovarian EMS. Global miRNA profiling was evaluated on 81 samples (EMS, TL and ECOC) from 44 patients. Principal component analysis and unsupervised clustering revealed two distinct clusters formed by ECOC and ovarian EMS samples, whereas TL were dispersed among the other two. Differential expression analysis (DEA) of TL vs. ovarian EMS, revealed 30 significantly upregulated miRNAs. Comparison of ECOC vs. TL samples yielded 118 significantly upregulated and 77 downregulated miRNAs. Finally, DEA of ECOC vs. ovarian EMS lesions yielded 200 upregulated and 128 downregulated miRNAs. Evaluation of miRNAs commonly deregulated between the three groups showed 14 shared upregulated miRNAs (miR-429, miR-425-5p, miR-200c-3p, miR-200c-5p, miR-200b-3p, miR-200a-3p, miR-183-5p, miR-182-5p, miR-141-5p, miR-141-3p, miR-96-5p, miR-93-5p, miR-10a-5p, miR-10a-3p) with a progressive increase in expression levels, from ovarian EMS to TL and ultimately to ECOC. The identified miRNA expression profiles associated with the progression from ovarian EMS, TL and ECOC provide valuable insights into the molecular progression from benign to malignant lesions and could represent potential biomarkers for the early detection of ECOC.