Abel Decmann1, Pal Perge 1, Gabor Nyiro2, Otto Darvasi3, Istvan Liko3, Katalin Borka4, Tamas Micsik5, Attila Patócs3, Peter Igaz1,2
1 2nd Department of Medicine, Faculty of Medicine, Semmelweis
University, Budapest, Hungary
2 MTA-SE Molecular Medicine Research Group, Hungarian Academy of
Sciences and Semmelweis University, Budapest, Hungary
3 Hereditary Endocrine Tumors Research Group, Hungarian Academy
of Sciences and Semmelweis University, Budapest, Hungary
4 2nd Department of Pathology, Faculty of Medicine, Semmelweis University, Budapest, Hungary
5 1st Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, Budapest, Hungary
Introduction: Adrenal myelolipoma (AML) is the second most common primary benign tumor of the adrenal gland. It is composed of variable amounts of adipose tissue and hematopoietic elements. Thus, it is sometimes challenging to differentiate AML from adrenocortical cancer (ACC). To date there is no available biomarker in the diagnostics of adrenal myelolipoma. MicroRNAs have been identified as promising biomarkers in many tumors, including adrenal neoplasms, but the microRNA expression of AML has not been investigated, yet.
Aim: Our aim was to identify microRNA biomarkers in adrenal myelolipoma, adrenocortical adenoma (ACA) and adrenocortical carcinoma through performing large scale microRNA expression profiling.
Methods: Our discovery cohort contained altogether 30 formalin-fixed paraffin-embedded archived tissue of adrenal myelolipoma, adrenocortical adenoma and adrenocortical carcinoma 10 samples each. Next-generation sequencing was performed by Illumina MiSeq. The independent validation cohort contained further samples of 15 AML, 14 ACA and 12 ACC. Significantly differentially expressed microRNAs were validated by real-time qPCR.
Results: With NGS, relatively overexpressed levels of miR-451a, miR-486-5p, miR-363-3p and miR-150-5p were found in AML compared to ACC and ACA. We have found up-regulated miR-184, miR-483-5p, miR-483-3p, miR-431-5p and miR-183-5p in ACC samples compared to AML and ACA. Validation confirmed the overexpression of all the 4 microRNAs in AML compared to ACC and ACA, whereas miR-184 was found to be the only miRNA that is significantly overexpressed in ACC compared both to AML and ACA. Significant overexpression of miR-483-5p, miR-483-3p, miR-183-5p was found in ACC compared to AML and ACA.
Conclusion: Up-regulated miR-451a, miR-486-5p, miR-363-3p, miR-150-5p might be a potential tissue marker of adrenal myelolipoma. A remarkable result of our study is that the expression of miR-483-5p in AML and ACC was not significantly different. This finding is notable, as miR-483-5p is considered to be the best marker of adrenocortical carcinoma so far.
Doctoral School: Clinical Medicine (No. 2)
Program: Hormonal mechanisms (No. 13)
Supervisor: Dr. Peter Igaz