Integrative molecular bioinformatics study of human adrenocortical tumors

MicroRNA, tissue-specific target prediction, and pathway analysis

Zsófia Tömböl, Peter M. Szabó, Viktor Molnár, Zoltán Wiener, Gergely Tölgyesi, János Horányi, Peter Riesz, Peter Reismann, A. Patócs, István Likó, Rolf Christian Gaillard, A. Falus, K. Rácz, P. Igaz

Research output: Contribution to journalArticle

117 Citations (Scopus)

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 dCTmiR-511 and dCTmiR-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.

Original languageEnglish
Pages (from-to)895-906
Number of pages12
JournalEndocrine-Related Cancer
Volume16
Issue number3
DOIs
Publication statusPublished - Sep 2009

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Computational Biology
MicroRNAs
Adenoma
Adrenocortical Carcinoma
Neoplasms
Messenger RNA
Hydrocortisone
Software
Biomarkers
Sensitivity and Specificity

ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism

Cite this

Integrative molecular bioinformatics study of human adrenocortical tumors : MicroRNA, tissue-specific target prediction, and pathway analysis. / Tömböl, Zsófia; Szabó, Peter M.; Molnár, Viktor; Wiener, Zoltán; Tölgyesi, Gergely; Horányi, János; Riesz, Peter; Reismann, Peter; Patócs, A.; Likó, István; Gaillard, Rolf Christian; Falus, A.; Rácz, K.; Igaz, P.

In: Endocrine-Related Cancer, Vol. 16, No. 3, 09.2009, p. 895-906.

Research output: Contribution to journalArticle

Tömböl, Z, Szabó, PM, Molnár, V, Wiener, Z, Tölgyesi, G, Horányi, J, Riesz, P, Reismann, P, Patócs, A, Likó, I, Gaillard, RC, Falus, A, Rácz, K & Igaz, P 2009, 'Integrative molecular bioinformatics study of human adrenocortical tumors: MicroRNA, tissue-specific target prediction, and pathway analysis', Endocrine-Related Cancer, vol. 16, no. 3, pp. 895-906. https://doi.org/10.1677/ERC-09-0096
Tömböl, Zsófia ; Szabó, Peter M. ; Molnár, Viktor ; Wiener, Zoltán ; Tölgyesi, Gergely ; Horányi, János ; Riesz, Peter ; Reismann, Peter ; Patócs, A. ; Likó, István ; Gaillard, Rolf Christian ; Falus, A. ; Rácz, K. ; Igaz, P. / Integrative molecular bioinformatics study of human adrenocortical tumors : MicroRNA, tissue-specific target prediction, and pathway analysis. In: Endocrine-Related Cancer. 2009 ; Vol. 16, No. 3. pp. 895-906.
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