title: Integrative molecular bioinformatics study of human adrenocortical tumors: microRNA, tissue-specific target prediction, and pathway analysis.
abstract: MicroRNAs (miRs) are involved in the pathogenesis of several neoplasms; however, there are no data on their expression patterns and possible roles in adrenocortical tumors. Our objective was to study adrenocortical tumors by an integrative bioinformatics analysis involving miR and transcriptomics profiling, pathway analysis, and a novel, tissue-specific miR target prediction approach. Thirty-six tissue samples including normal adrenocortical tissues, benign adenomas, and adrenocortical carcinomas (ACC) were studied by simultaneous miR and mRNA profiling. A novel data-processing software was used to identify all predicted miR-mRNA interactions retrieved from PicTar, TargetScan, and miRBase. Tissue-specific target prediction was achieved by filtering out mRNAs with undetectable expression and searching for mRNA targets with inverse expression alterations as their regulatory miRs. Target sets and significant microarray data were subjected to Ingenuity Pathway Analysis. Six miRs with significantly different expression were found. miR-184 and miR-503 showed significantly higher, whereas miR-511 and miR-214 showed significantly lower expression in ACCs than in other groups. Expression of miR-210 was significantly lower in cortisol-secreting adenomas than in ACCs. By calculating the difference between dCT(miR-511) and dCT(miR-503) (delta cycle threshold), ACCs could be distinguished from benign adenomas with high sensitivity and specificity. Pathway analysis revealed the possible involvement of G2/M checkpoint damage in ACC pathogenesis. To our knowledge, this is the first report describing miR expression patterns and pathway analysis in sporadic adrenocortical tumors. miR biomarkers may be helpful for the diagnosis of adrenocortical malignancy. This tissue-specific target prediction approach may be used in other tumors too.
authors: Second Department of Medicine, Faculty of Medicine, Semmelweis University, Szentkirályi Street 46, H-1088 Budapest, Hungary.
authors: Zsófia
authors: Z
authors: Tömböl
authors: Peter M
authors: PM
authors: Szabó
authors: Viktor
authors: V
authors: Molnár
authors: Zoltán
authors: Z
authors: Wiener
authors: Gergely
authors: G
authors: Tölgyesi
authors: János
authors: J
authors: Horányi
authors: Peter
authors: P
authors: Riesz
authors: Peter
authors: P
authors: Reismann
authors: Attila
authors: A
authors: Patócs
authors: István
authors: I
authors: Likó
authors: Rolf-Christian
authors: RC
authors: Gaillard
authors: András
authors: A
authors: Falus
authors: Károly
authors: K
authors: Rácz
authors: Peter
authors: P
authors: Igaz
mesh_terms: D000236:Adenoma / Q000175:diagnosis / Q000235:genetics*; D000306:Adrenal Cortex Neoplasms / Q000175:diagnosis / Q000235:genetics*; D018268:Adrenocortical Carcinoma / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D019295:Computational Biology / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005544:Forecasting / Q000379:methods; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D008954:Models, Biological; D009928:Organ Specificity / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs