ECE2014 Oral Communications Endocrine Tumours (5 abstracts)
Blood-borne and tissue microRNAs in adrenocortical tumours: affected pathways and diagnostic relevance
Peter Igaz 1 , Diana Rita Szabo 1 , Adrienn Zsippai 1 , Peter M Szabo 2 , Zoltan Nagy 1 , Miklos Toth 1 , Michaela Luconi 3 , Massimo Mannelli 3 , Attila Patocs 2, & Karoly Racz 1,
12nd Department of Medicine, Semmelweis University, Budapest, Hungary; 2Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary; 3Department of Clinical Physiopathology, Endocrinology Unit, University of Florence, Florence, Italy; 4HAS-SE “Lendulet” Hereditary Endocrine Tumors Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
Background: The differential expression of tissue microRNAs in benign and malignant adrenocortical tumours has been described in several studies including ours. Novel data show that microRNAs are also present in the bloodstream and can be exploited as minimally invasive markers of malignancy.
Objective: To analyze the microRNAs expressed in different studies by an in silico approach and to establish the molecular pathways affected. Furthermore, circulating counterparts of selected tissue microRNAs were examined to evaluate their applicability as markers of malignancy.
Methods: MicroRNA and mRNA datasets have been subjected to tissue specific target prediction by an own software. Pathway analysis was performed by Ingenuity Pathway Analysis. Blood-borne counterparts of eight microRNAs reported as significantly differentially expressed in tissues have been studied by real-time qRT-PCR of total RNA isolated from plasma samples of patients with adrenocortical adenomas (ACA) and adrenocortical cancer (ACC).
Results: Eighty-five molecular pathways have been found in the ACA–ACC comparison that might be affected by the significantly differentially expressed tissue microRNAs commonly altered in at least two studies. These include novel pathways e.g. interleukin and growth factor signalling, integrin signalling, aryl hydrocarbon receptor signalling, etc. From the eight blood-borne microRNAs tested, five (hsa-miR-483-5p, hsa-miR-181b, hsa-miR-100, hsa-miR-210, hsa-miR-184) showed significant overexpression in ACC plasma samples relative to ACA using hsa-miR-16 as reference gene. By ROC analysis, the combination of dCThsa-miR-210-dCThsa-miR-181b and dCThsa-miR-100/dCThsa-miR-181b showed the best sensitivity and specificity among blood-borne microRNAs as markers of malignancy and these are different from the best markers reported in adrenocortical tissues to date.
Conclusions: The numerous pathways affected may include pathways that might even represent potential novel therapeutic targets. Significant differences in expression of blood-borne plasma microRNAs have been established between ACA and ACC, but further studies will be needed to confirm their applicabililty in the clinical setting.
Volume 35
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