MicroRNA-based signatures impacting clinical course and biology of ovarian cancer: a miRNOmics study

Abstract Background In Western countries, ovarian cancer (OC) still represents the leading cause of gynecological cancer-related deaths, despite the remarkable gains in therapeutical options. Novel biomarkers of early diagnosis, prognosis definition and prediction of treatment outcomes are of pivotal importance. Prior studies have shown the potentials of micro-ribonucleic acids (miRNAs) as biomarkers for OC and other cancers. Methods We focused on the prognostic and/or predictive potential of miRNAs in OC by conducting a comprehensive array profiling of miRNA expression levels in ovarian tissue samples from 17 non-neoplastic controls, and 60 tumor samples from OC patients treated at the Regina Elena National Cancer Institute (IRE). A set of 54 miRNAs with differential expression in tumor versus normal samples (T/N-deregulated) was identified in the IRE cohort and validated against data from the Cancer Genoma Atlas (TCGA) related to 563 OC patients and 8 non-neoplastic controls. The prognostic/predictive role of the selected 54 biomarkers was tested in reference to survival endpoints and platinum resistance (P-res). Results In the IRE cohort, downregulation of the 2 miRNA-signature including miR-99a-5p and miR-320a held a negative prognostic relevance, while upregulation of miR-224-5p was predictive of less favorable event free survival (EFS) and P-res. Data from the TCGA showed that downregulation of 5 miRNAs, i.e., miR-150, miR-30d, miR-342, miR-424, and miR-502, was associated with more favorable EFS and overall survival outcomes, while miR-200a upregulation was predictive of P-res. The 9 miRNAs globally identified were all included into a single biologic signature, which was tested in enrichment analysis using predicted/validated miRNA target genes, followed by network representation of the miRNA-mRNA interactions. Conclusions Specific dysregulated microRNA sets in tumor tissue showed predictive/prognostic value in OC, and resulted in a promising biological signature for this disease.

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Prognostic Values and Prospective Pathway Signaling of miR-30a in Ovarian Cancer: A Study Based on Gene Expression Omnibus and Bioinformatics Analysis

10.21203/rs.3.rs-27014/v1 ◽

2020 ◽

Author(s):

Weijia Lu ◽

Yunyu Wu ◽

CanXiong Lu ◽

Ting Zhu ◽

ZhongLu Ren ◽

...

Keyword(s):

Gene Expression ◽

Ovarian Cancer ◽

Target Genes ◽

Ovarian Tissue ◽

Differentially Expressed Gene ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

Hub Genes ◽

Protein Protein Interaction ◽

Public Data

Abstract Objective MicroRNAs (MiRNAs) is considered to play an important role in the occurrence and development of ovarian cancer(OC). Although miRNAs has been widely recognized in ovarian cancer, the role of hsa-miR-30a-5p (miR-30a) in OC has not been fully elucidated. Methods Through the analysis of public data sets in Gene Expression Omnibus (GEO) database and literature review, the significance of miR-30a expression in OC is evaluated. Three mRNA datasets of OC and normal ovarian tissue, GSE14407, GSE18520 and GSE36668, were downloaded from GEO to find the differentially expressed gene (DEG). Then the target genes of hsa-miR-30a-5p were predicted by miRWALK3.0 and TargetScan. Then, the gene overlap between DEG and the predicted target genes of miR-30a in OC was analyzed by Gene Ontology (GO) enrichment analysis. Protein-protein interaction (PPI) network was constructed by STRING and Cytoscape, and the effect of HUB gene on the prognosis of OC was analyzed. Results A common pattern of up-regulation of miR-30a in OC was found. A total of 225 DEG, were identified, both OC-related and miR-30a-related. Many DEG are enriched in the interactions of intracellular matrix tissue, ion binding and biological process regulation. Among the 10 major Hub genes analyzed by PPI, five Hub genes were significantly related to the overall poor survival of OC patients, in which the low expression of ESR1 ,MAPK10, Tp53 and the high expression of YKT ,NSF were related to poor prognosis of OC.

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Bioinformatics Analysis of Prognostic value and prospective Pathway signal of miR-30a in Ovarian Cancer

10.21203/rs.3.rs-30974/v1 ◽

2020 ◽

Author(s):

Weijia Lu ◽

Yunyu Wu ◽

CanXiong Lu ◽

Ting Zhu ◽

ZhongLu Ren ◽

...

Keyword(s):

Ovarian Cancer ◽

Target Genes ◽

Ovarian Tissue ◽

Critical Role ◽

Differentially Expressed Gene ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

Hub Genes ◽

Protein Protein Interaction ◽

Go Enrichment

Abstract Objective: MicroRNAs (MiRNAs) is thought to play an critical role in the initiation and progress of ovarian cancer(OC). Although miRNAs has been widely recognized in ovarian cancer, the role of hsa-miR-30a-5p (miR-30a) in OC has not been fully elucidated.Methods:Three mRNA datasets of normal ovarian tissue and OC, GSE18520 ,GSE14407 and GSE36668, were downloaded from Gene Expression Omnibus(GEO) to find the differentially expressed gene (DEG). Then the target genes of hsa-miR-30a-5p were predicted by miRWALK3.0 and TargetScan. Then, the gene overlap between DEG and the predicted target genes of miR-30a in OC was analyzed by Gene Ontology (GO) enrichment analysis. Protein-protein interaction (PPI) network was conducted by STRING and Cytoscape, and the effect of HUB gene on the outcome of OC was analyzed.Results：A common pattern of up-regulation of miR-30a in OC was found. A total of 225 DEG, were identified, both OC-related and miR-30a-related. Many DEG are enriched in the interactions of intracellular matrix tissue, ion binding and biological process regulation. Among the 10 major Hub genes analyzed by PPI, five Hub genes were significantly related to the overall poor survival of OC patients, in which the low expression of ESR1 ,MAPK10, Tp53 and the high expression of YKT ,NSF were related to poor prognosis of OC.Conclusion：Our results indicate that miR-30a is of significance for the biological progress of OC.

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Bioinformatics analysis of prognostic value and prospective pathway signal of miR-30a in ovarian cancer

Journal of Ovarian Research ◽

10.1186/s13048-020-00722-8 ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Weijia Lu ◽

Yunyu Wu ◽

Can Xiong Lu ◽

Ting Zhu ◽

Zhong Lu Ren ◽

...

Keyword(s):

Ovarian Cancer ◽

Target Genes ◽

Ovarian Tissue ◽

Critical Role ◽

Differentially Expressed Gene ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

Hub Genes ◽

Protein Protein Interaction ◽

Go Enrichment

Abstract Objective MicroRNAs (MiRNAs) is thought to play a critical role in the initiation and progress of ovarian cancer (OC). Although miRNAs has been widely recognized in ovarian cancer, the role of hsa-miR-30a-5p (miR-30a) in OC has not been fully elucidated. Methods Three mRNA datasets of normal ovarian tissue and OC, GSE18520,GSE14407 and GSE36668, were downloaded from Gene Expression Omnibus (GEO) to find the differentially expressed gene (DEG). Then the target genes of hsa-miR-30a-5p were predicted by miRWALK3.0 and TargetScan. Then, the gene overlap between DEG and the predicted target genes of miR-30a in OC was analyzed by Gene Ontology (GO) enrichment analysis. Protein-protein interaction (PPI) network was conducted by STRING and Cytoscape, and the effect of HUB gene on the outcome of OC was analyzed. Results A common pattern of up-regulation of miR-30a in OC was found. A total of 225 DEG, were identified, both OC-related and miR-30a-related. Many DEG are enriched in the interactions of intracellular matrix tissue, ion binding and biological process regulation. Among the 10 major Hub genes analyzed by PPI, five Hub genes were significantly related to the overall poor survival of OC patients, in which the low expression of ESR1,MAPK10, Tp53 and the high expression of YKT,NSF were related to poor prognosis of OC. Conclusion Our results indicate that miR-30a is of significance for the biological progress of OC.

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Proteomic Profile Mapping and Differential Expression of Protein in Ovarian Cancer

Sains Malaysiana ◽

10.17576/jsm-2021-5012-17 ◽

2021 ◽

Vol 50 (12) ◽

pp. 3667-3681

Author(s):

Ambreen Tauseef ◽

Asima Karim ◽

Gulfam Ahmad ◽

Qurratulann Afza Gardner ◽

Muhammad Waheed Akhtar

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Ovarian Tissue ◽

Protein Profile ◽

Protein Profiling ◽

Differentially Expressed ◽

P Value ◽

Differentially Expressed Proteins ◽

Tissue Samples ◽

Novel Biomarkers

This study aimed to characterize differentially expressed proteins in malignant ovarian tissue to find out potential novel biomarkers in ovarian cancer (OC). We enrolled 20 ovarian cancer patients (40-65 years) and an equal number of age-matched healthy women to get malignant and healthy ovarian tissue samples for protein extraction and quantification after tissue lysis. The protein profile was analyzed using two-dimensional gel electrophoresis followed by MALDI-TOF mass spectrometry. Based on the information thus obtained, the proteins were identified using the relevant software and protein databank to analyze the malignant and non-malignant ovarian tissue samples (n = 20/group). In this proteomic analysis of the ovarian tissue, 112 proteins were detected. Based on a minimum of ≥ 1.5-fold expression difference (p-value ≤ 0.05; FDR ≤ 0.05 and PMF ≥ 79), 17 proteins were found to be upregulated while 27 were downregulated in the malignant ovarian tissue. Six of these proteins have not been previously reported in ovarian cancer. Out of these, three are upregulated while the other three are downregulated. The upregulated proteins are centrosomal protein of 290 kDa (Cep290), uncharacterized protein C1orf109 (C1orf109) and GTPase-activating Rap/Ran-GAP domain-like protein 3 (GARNL3), and the three downregulated proteins identified are actin-related protein 3 (ARP3), cytosolic carboxypeptidase 3 (AGBL3) and NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10 (NDUFA10). This proteomic mapping not only provides data on protein profiling of ovarian cancer in Pakistani population for the first time but also reports six novel differentially expressed proteins, which have not been previously reported in ovarian cancer patients. They may serve as potential novel biomarkers after further validation for early diagnosis and prognosis of ovarian cancer. It also provides additional data to improve existing knowledge of already reported protein ovarian cancer biomarkers.

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Transcriptome Analyses Identify Potential Key microRNAs and Their Target Genes Contributing to Ovarian Reserve

International Journal of Molecular Sciences ◽

10.3390/ijms221910819 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10819

Author(s):

Yoon-Young Kim ◽

Kwang-Soo Kim ◽

Yong-Jin Kim ◽

Sung-Woo Kim ◽

Hoon Kim ◽

...

Keyword(s):

Ovarian Reserve ◽

Target Genes ◽

Ovarian Tissue ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Regulatory Function ◽

Tissue Samples ◽

Mirna Sequencing ◽

Regulator Genes ◽

The Impact

Female endocrinological symptoms, such as premature ovarian inefficiency (POI) are caused by diminished ovarian reserve and chemotherapy. The etiology of POI remains unknown, but this can lead to infertility. This has accelerated the search for master regulator genes or other molecules that contribute as enhancers or silencers. The impact of regulatory microRNAs (miRNAs) on POI has gained attention; however, their regulatory function in this condition is not well known. RNA sequencing was performed at four stages, 2-(2 W), 6-(6 W), 15-(15 W), and 20-(20 W) weeks, on ovarian tissue samples and 5058 differentially expressed genes (DEGs) were identified. Gene expression and enrichment were analyzed based on the gene ontology and KEGG databases, and their association with other proteins was assessed using the STRING database. Gene set enrichment analysis was performed to identify the key target genes. The DEGs were most highly enriched in 6 W and 15 W groups. Figla, GDF9, Nobox, and Pou51 were significantly in-creased at 2 W compared with levels at 6 W and 20 W, whereas the expression of Foxo1, Inha, and Taf4b was significantly de-creased at 20 W. Ccnd2 and Igf1 expression was maintained at similar levels in each stage. In total, 27 genes were upregulated and 26 genes interacted with miRNAs; moreover, stage-specific upregulated and downregulated interactions were demonstrated. Increased and decreased miRNAs were identified at each stage in the ovaries. The constitutively expressed genes, Ccnd2 and Igf1, were identified as the major targets of many miRNAs (p < 0.05), and Fshr and Foxo3 interacted with miRNAs, namely mmu-miR-670-3p and mmu-miR-153-3p. miR-26a-5p interacted with Piwil2, and its target genes were downregulated in the 20 W mouse ovary. In this study, we aimed to identify key miRNAs and their target genes encompassing the reproductive span of mouse ovaries using mRNA and miRNA sequencing. These results indicated that gene sets are regulated in the reproductive stage-specific manner via interaction with miRNAs. Furthermore, consistent expression of Ccnd2 and Igf1 is considered crucial for the ovarian reserve and is regulated by many interactive miRNAs.

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Epigenetic Mechanism and Survival Prognosis Analysis of Serum Exosomes from Ovarian Cancer Patients based on Sequencing Technology and Bioinformatics

10.21203/rs.3.rs-981954/v1 ◽

2021 ◽

Author(s):

Li Xia ◽

Huang He

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Target Genes ◽

Epigenetic Modification ◽

Gene Prediction ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Survival Prognosis ◽

Signaling Axis ◽

Serum Exosomes

Abstract Backguound: To screen the signaling axis of epigenetic modification in serum exosomes of ovarian cancer patients based on sequencing technology and raw signal analysis, in depth study of the potential mechanism of action of ovarian cancer, prediction of potential therapeutic targets and survival prognosis analysis of potential targets.Methods: Serum exosomes from three ovarian cancer patients were selected as the experimental group, and serum exosomes from three uterine fibroid patients as the control group, and whole transcriptome of serum exosomes was performed to obtain differentially expressed lncRNA and mRNA in ovarian cancer,The miRcode database and miRNA target gene prediction website were used to predict the target genes, Cytoscape software was used to draw a ceRNA network model of epigenetic modification of ovarian cancer serum exosomes, and the R language was used for GO and KEGG enrichment analysis of the target genes. Finally, the TCGA website was used to download clinical and expression data related to ovarian cancer, and the common potential target genes obtained in the previous period were analyzed for survival。Results: A total of 117 differentially expressed lncRNAs as well as 513 differentially expressed mRNAs (P < 0.05, |log2 FC|≥ 1.0) were obtained by combining sequencing data and raw signal analysis, and 841 predicted target genes were reciprocally mapped by combining mircode database and miRNA target gene prediction website, resulting in 11 potential target genes related to ovarian cancer (FGFR3, BMPR1B, TRIM29, FBN2, PAPPA, CCDC58, IGSF3, FBXO10, GPAM, HOXA10, LHFPL4), and survival prognosis analysis of the above 11 target genes revealed that the survival curve was statistically significant (P < 0.05) for HOXA10 only genes, but not for the other genes, and through enrichment analysis, we found that the above target genes were mainly involved in biological processes such as regulation of transmembrane receptor protein kinase activity, structural molecule activity with elasticity, transforming growth factor - activated receptor activity, and GABA receptor binding, and were mainly enriched in signaling pathways regulating stem cell pluripotency, bladder cancer, glycerolipid metabolism, central carbon metabolism of cancer, tyrosine stimulation to EGFR in signaling pathways such as resistance to enzyme inhibitors.Conclusions: The serum exosomal DIO3OS-hsa-miR-27a-3p-HOXA10 epigenetic modification signaling axis affects ovarian cancer development and disease survival prognosis by targeting transcriptional dysregulation pathways in cancer.

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Development of a Genomic Signatures-Based Predictor of Initial Platinum-Resistance in Advanced High-Grade Serous Ovarian Cancer Patients

Frontiers in Oncology ◽

10.3389/fonc.2020.625866 ◽

2021 ◽

Vol 10 ◽

Author(s):

Yuan Li ◽

Xiaolan Zhang ◽

Yan Gao ◽

Chunliang Shang ◽

Bo Yu ◽

...

Keyword(s):

Ovarian Cancer ◽

Predictive Accuracy ◽

Predictive Performance ◽

Platinum Resistance ◽

High Grade ◽

Serous Ovarian Cancer ◽

Single Nucleotide Variants ◽

Tissue Samples ◽

Platinum Sensitive ◽

Platinum Based Chemotherapy

BackgroundHigh grade serous ovarian cancer (HGSOC) is the most common subtype of ovarian cancer. Although platinum-based chemotherapy has been the cornerstone for HGSOC treatment, nearly 25% of patients would have less than 6 months of interval since the last platinum chemotherapy, referred to as platinum-resistance. Currently, no precise tools to predict platinum resistance have been developed yet.MethodsNinety-nine HGSOC patients, who have finished cytoreductive surgery and platinum-based chemotherapy in Peking University Third Hospital from 2018 to 2019, were enrolled. Whole-genome sequencing (WGS) and whole-exome sequencing (WES) were performed on the collected tumor tissue samples to establish a platinum-resistance predictor in a discovery cohort of 57 patients, and further validated in another 42 HGSOC patients.ResultsA high prevalence of alterations in DNA damage repair (DDR) pathway, including BRCA1/2, was identified both in the platinum-sensitive and resistant HGSOC patients. Compared with the resistant subgroup, there was a trend of higher prevalence of homologous recombination deficiency (HRD) in the platinum-sensitive subgroup (78.95% vs. 47.37%, p=0.0646). Based on the HRD score, microhomology insertions and deletions (MHID), copy number changes load, duplication load of 1–100 kb, single nucleotide variants load, and eight other mutational signatures, a combined predictor of platinum-resistance, named as DRDscore, was established. DRDscore outperformed in predicting the platinum-sensitivity than the previously reported biomarkers with a predictive accuracy of 0.860 at a threshold of 0.7584. The predictive performance of DRDscore was validated in an independent cohort of 42 HGSOC patients with a sensitivity of 90.9%.ConclusionsA multi-genomic signature-based analysis enabled the prediction of initial platinum resistance in advanced HGSOC patients, which may serve as a novel assessment of platinum resistance, provide therapeutic guidance, and merit further validation.

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The target genes research for diagnosis, therapy and prognosis in cases with ovarian cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.16060 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 16060-16060

Author(s):

E. V. Bakhidze ◽

A. V. Malek ◽

A. V. Belyaeva

Keyword(s):

Gene Expression ◽

Ovarian Cancer ◽

Target Genes ◽

Ovarian Tissue ◽

In Situ Hybridisation ◽

Genetic Alterations ◽

Surface Epithelium ◽

Low Grade ◽

Grade Tumour ◽

Tumour Differentiation

16060 Background: Epithelial ovarian cancer has one of the worst prognoses among gynecologic malignancies. Molecular genetic analyses of ovarian cancers have uncovered genetic alterations of several genes. Normal tissues were readily distinguished from tumor tissues. These studies identified several genes, such as High mobility group A2 (HMG A2) proteins. The expression of HMG A2 gene is detected in foetal stage of human development and stopped in normal adult tissues. Elevation of the HMG A2 gene expression was shown for several human malignant tumours. Targeted supression of HMG A2 protein synthesis can be one of important directions for anti-tumour therapy in cases of ovarian cancer Methods: The HMG A2 gene expression was searched in 48 flash-frozen samples of ovarian serous papillary adenocarcinoma and 12 samples of normal ovarian tissue. The HMG A2 gene expression was investigated by RNA in situ hybridisation. Results: High and middle level of HMG A2 gene expression was shown in 37 from 48 (77%) ovarian cancer samples. HMG A2 mRNA was not detected in normal ovarian surface epithelium. Low grade tumour differentiation (G3) was detected in 24 cases from 37 (64,9%), middle differentiation (G2) was detected in 12 cases (32,4%) and high grade differentiation (G1) was detected in 1 case (2,7%). Conclusions: HMG A2 high expression is a typical and important feature of serouse type of ovarian carcinoma. High level of HMG A2 gene expression correlate with low grade tumour differentiation. No significant financial relationships to disclose.

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Circulating miRNA Profiling in Plasma Samples of Ovarian Cancer Patients

International Journal of Molecular Sciences ◽

10.3390/ijms20184533 ◽

2019 ◽

Vol 20 (18) ◽

pp. 4533 ◽

Cited By ~ 8

Author(s):

András Penyige ◽

Éva Márton ◽

Beáta Soltész ◽

Melinda Szilágyi-Bónizs ◽

Róbert Póka ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Patients ◽

Target Genes ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Cancer Development ◽

Plasma Samples ◽

Circulating Mirna ◽

Differentially Expressed Mirnas ◽

Potential Biomarkers

Ovarian cancer is one of the most common cancer types in women characterized by a high mortality rate due to lack of early diagnosis. Circulating miRNAs besides being important regulators of cancer development could be potential biomarkers to aid diagnosis. We performed the circulating miRNA expression analysis in plasma samples obtained from ovarian cancer patients stratified into FIGO I, FIGO III, and FIGO IV stages and from healthy females using the NanoString quantitative assay. Forty-five miRNAs were differentially expressed, out of these 17 miRNAs showed significantly different expression between controls and patients, 28 were expressed only in patients, among them 19 were expressed only in FIGO I patients. Differentially expressed miRNAs were ranked by the network-based analysis to assess their importance. Target genes of the differentially expressed miRNAs were identified then functional annotation of the target genes by the GO and KEGG-based enrichment analysis was carried out. A general and an ovary-specific protein–protein interaction network was constructed from target genes. Results of our network and the functional enrichment analysis suggest that besides HSP90AA1, MYC, SP1, BRCA1, RB1, CFTR, STAT3, E2F1, ERBB2, EZH2, and MET genes, additional genes which are enriched in cell cycle regulation, FOXO, TP53, PI-3AKT, AMPK, TGFβ, ERBB signaling pathways and in the regulation of gene expression, proliferation, cellular response to hypoxia, and negative regulation of the apoptotic process, the GO terms have central importance in ovarian cancer development. The aberrantly expressed miRNAs might be considered as potential biomarkers for the diagnosis of ovarian cancer after validation of these results in a larger cohort of ovarian cancer patients.

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A loss of microRNA expression as a characterization of synchronous peritoneal secondary localizations of epithelial ovarian cancer as compared to primary tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.11037 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 11037-11037

Author(s):

Delia Mezzanzanica ◽

Loris De Cecco ◽

Daniela Califano ◽

Simona Losito ◽

Marina Bagnoli ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Target Genes ◽

Ectopic Expression ◽

Differentially Expressed ◽

Platinum Resistance ◽

Primary Tumors ◽

Gynecological Malignancy ◽

Primary Surgery

11037 Background: Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy and one of the most challenging areas of cancer research being a highly heterogeneous disease difficult to diagnose and treat. EOC has a peculiar dissemination process due to the sloughing-off of cells from primary tumors and their spread throughout the peritoneal cavity. A better characterization of the mechanism involved in tumor spreading might help in design new therapeutic intervention. Methods: Forty-four couples of chemo naïf primary tumors and synchronous secondary peritoneal localizations, obtained at primary surgery from MITO2 clinical trial, have been profiled for microRNA (miRNA) expression on an Agilent Platform. Total RNA was extracted from formalin-fixed paraffin embedded tissues. An independent validation set of samples with similar characteristics, has been collected at INT Milan. Results: By class comparison analysis, imposing a false discovery rate <10%,45 miRNAs were identified as differentially expressed: 32 down-modulated and 13 up-modulated in secondary localizations compared to primary tumors. Among the miRNAs down-modulated in the secondary localizations we detected most of the miRNA belonging to the Xq27.3 cluster, whose low expression we previously described to be associated with EOC early relapse, and a number of miRNAs related to epithelial/mesenchimal transition (EMT) whose modulation could be related to dissemination of the disease and response to drug treatment. In particularly loss of has-miR-506 resulted associated to platinum resistance since its ectopic expression in EOC cell lines increased their sensitivity to the drug. Furthermore preliminary data indicated that has-miR-506 regulated N-cadherin linking its modulation to EMT. Conclusions: To our knowledge, the present study is the first attempt to characterize a miRNA signature differentially expressed between EOC primary tumors and synchronous secondary peritoneal localizations. The validation of the miRNA profile as well as of target genes might help in elucidating EOC dissemination mechanisms and in defining possible new therapeutic targets.

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