nach oben

Erschienen in:

03.01.2018 | Endocrine Genetics/Epigenetics

Analysis of circulating extracellular vesicle-associated microRNAs in cortisol-producing adrenocortical tumors

verfasst von: Pál Perge, Ábel Decmann, Raffaele Pezzani, Irina Bancos, Ambrogio Fassina, Michaela Luconi, Letizia Canu, Miklós Tóth, Marco Boscaro, Attila Patócs, Peter Igaz

Erschienen in: Endocrine | Ausgabe 2/2018

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Circulating microRNAs (miRNA) have been described in patients with adrenocortical tumors, but the expression of miRNAs in non-functioning and cortisol-producing tumors has not been yet compared. Therefore, the objective of this study was to evaluate the expression of plasma extracellular vesicle (EV)-associated microRNAs in patients with non-functioning adrenocortical adenoma (NFA), cortisol-producing adrenocortical adenoma (CPA) and cortisol-producing adrenocortical carcinoma (CP-ACC).

Methods

Preoperative plasma EV samples of 13 NFAs, 13 CPAs and 9 CP-ACCs were subjected to extracellular vesicle isolation. miRNAs were investigated by targeted quantitative real-time PCR normalized to cel-miR-39 as reference. Five miRNAs have been selected for this analysis based on the previous studies including hsa-miR-22-3p, hsa-miR-27a-3p, hsa-miR-210-3p, hsa-miR-320b and hsa-miR-375.

Results

We have observed significant overrepresentation of three miRNAs in both CPA and CP-ACC relative to NFA: hsa-miR-22-3p (p < 0.01 and p < 0.0001, respectively), hsa-miR-27a-3p (p < 0.05 in both comparisons) and hsa-miR-320b (p < 0.05 and p < 0.0001, respectively). Hsa-miR-320b has been significantly overrepresented in CP-ACC relative to CPA (p < 0.01). Hsa-miR-210-3p turned out to be significantly overrepresented only in CP-ACC compared to NFA (p < 0.05). Significant correlation was revealed between circulating miRNA concentrations and urinary free cortisol values for hsa-miR-22-3p, hsa-miR-27a-3p and hsa-miR-320b (p < 0.0001 for all) and cortisol after low-dose dexamethasone test for hsa-miR-22-3p and hsa-miR-320b (p < 0.05). Hsa-miR-27a-3p has been significantly stimulated by low-dose dexamethasone test (p < 0.05).

Conclusions

EV-associated miRNAs are differentially expressed in different non-functioning and cortisol-producing adrenocortical tumors.

Nur mit Berechtigung zugänglich

M. Terzolo, A. Stigliano, I. Chiodini, P. Loli, L. Furlani, G. Arnaldi, G. Reimondo, A. Pia, V. Toscano, M. Zini, G. Borretta, E. Papini, P. Garofalo, B. Allolio, B. Dupas, F. Mantero, A. Tabarin Italian Association of Clinical Endocrinologists AME position statement on adrenal incidentaloma. Eur. J. Endocrinol. 164, 851–870 (2011). https://doi.org/10.1530/EJE-10-1147 CrossRefPubMed

M. Terzolo, S. Bovio, A. Pia, G. Reimondo, A. Angeli, Management of adrenal incidentaloma. Best. Pract. Res. Clin. Endocrinol. Metab. 23, 233–243 (2009). https://doi.org/10.1016/j.beem.2009.04.001 CrossRefPubMed

P. Igaz, I. Igaz, Z. Nagy, G. Nyírő, P.M. Szabó, A. Falus, A. Patócs, K. Rácz, MicroRNAs in adrenal tumors: relevance for pathogenesis, diagnosis, and therapy. Cell. Mol. Life Sci. 72, 417–428 (2015). https://doi.org/10.1007/s00018-014-1752-7 CrossRefPubMed

L.K. Nieman, B.M.K. Biller, J.W. Findling, J. Newell-Price, M.O. Savage, P.M. Stewart, V.M. Montori, The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 93, 1526–1540 (2008). https://doi.org/10.1210/jc.2008-0125 CrossRefPubMedPubMedCentral

R. Libé, I. Borget, C.L. Ronchi, B. Zaggia, M. Kroiss, T. Kerkhofs, J. Bertherat, M. Volante, M. Quinkler, O. Chabre, M. Bala, A. Tabarin, F. Beuschlein, D. Vezzosi, T. Deutschbein, F. Borson-Chazot, I. Hermsen, A. Stell, C. Fottner, S. Leboulleux, S. Hahner, M. Mannelli, A. Berruti, H. Haak, M. Terzolo, M. Fassnacht, E. Baudin, ENSAT network: prognostic factors in stage III–IV adrenocortical carcinomas (ACC): an European Network for the Study of Adrenal Tumor (ENSAT) study. Ann. Oncol. 26, 2119–2225 (2015). https://doi.org/10.1093/annonc/mdv329 CrossRefPubMed

M. Fassnacht, M. Kroiss, B. Allolio, Update in adrenocortical carcinoma. J. Clin. Endocrinol. Metab. 98, 4551–4564 (2013). https://doi.org/10.1210/jc.2013-3020CrossRefPubMed

D.P. Bartel, MicroRNAs: target recognition and regulatory functions. Cel 136, 215–233 (2009). https://doi.org/10.1016/j.cell.2009.01.002 CrossRef

M.A. Cortez, C. Bueso-Ramos, J. Ferdin, G. Lopez-Berestein, A.K. Sood, G.A. Calin, MicroRNAs in body fluids--the mix of hormones and biomarkers. Nat. Rev. Clin. Oncol. 8, 467–477 (2011). https://doi.org/10.1038/nrclinonc.2011.76 CrossRefPubMedPubMedCentral

J. Zhang, S. Li, L. Li, M. Li, C. Guo, J. Yao, S. Mi., Exosome and exosomal MicroRNA: trafficking, sorting, and function. Genom. Proteom. Bioinforma. 13, 17–24 (2015). https://doi.org/10.1016/j.gpb.2015.02.001 CrossRef

10.

O. Chabre, R. Libé, G. Assie, O. Barreau, J. Bertherat, X. Bertagna, J.J. Feige, N. Cherradi, Serum miR-483-5p and miR-195 are predictive of recurrence risk in adrenocortical cancer patients. Endocr. Relat. Cancer 20, 579–594 (2013). https://doi.org/10.1530/ERC-13-0051 PubMed

11.

Z. Tömböl, P.M. Szabó, V. Molnár, Z. Wiener, G. Tölgyesi, J. Horányi, P. Riesz, P. Reismann, A. Patócs, I. Likó, R.C. Gaillard, A. Falus, K. Rácz, P. Igaz, Integrative molecular bioinformatics study of human adrenocortical tumors: microRNA, tissue-specific target prediction, and pathway analysis. Endocr. Relat. Cancer 16, 895–906 (2009). https://doi.org/10.1677/ERC-09-0096 CrossRefPubMed

12.

P.S. Soon, L.J. Tacon, A.J. Gill, C.P. Bambach, M.S. Sywak, P.R. Campbell, M.W. Yeh, S.G. Wong, R.J. Clifton-Bligh, B.G. Robinson, S.B. Sidhu, miR-195 and miR-483-5p identified as predictors of poor prognosis in adrenocortical cancer. Clin. Cancer Res. 15, 7684–7692 (2009). https://doi.org/10.1158/1078-0432.CCR-09-1587 CrossRefPubMed

13.

D.R. Szabó, M. Luconi, P.M. Szabó, M. Tóth, N. Szücs, J. Horányi, Z. Nagy, M. Mannelli, A. Patócs, K. Rácz, P. Igaz, Analysis of circulating microRNAs in adrenocortical tumors. Lab. Invest. 94, 331–339 (2014). https://doi.org/10.1038/labinvest.2013.148 CrossRefPubMed

14.

P. Perge, H. Butz, R. Pezzani, I. Bancos, Z. Nagy, K. Pálóczi, G. Nyírő, Á. Decmann, E. Pap, M. Luconi, M. Mannelli, E.I. Buzás, M. Tóth, M. Boscaro, A. Patócs, P. Igaz, Evaluation and diagnostic potential of circulating extracellular vesicle-associated microRNAs in adrenocortical tumors. Sci. Rep. 7, 5474 (2017). https://doi.org/10.1038/s41598-017-05777-0 CrossRefPubMedPubMedCentral

15.

D. Velázquez-Fernández, S. Caramuta, D.M. Özata, M. Lu, A. Höög, M. Bäckdahl, C. Larsson, W.O. Lui, J. Zedenius, MicroRNA expression patterns associated with hyperfunctioning and non-hyperfunctioning phenotypes in adrenocortical adenomas. Eur. J. Endocrinol. 170, 583–591 (2014). https://doi.org/10.1530/EJE-13-0817 CrossRefPubMed

16.

I. Igaz, G. Nyírő, Z. Nagy, H. Butz, Z. Nagy, P. Perge, P. Sahin, M. Tóth, K. Rácz, P. Igaz, A. Patócs, Analysis of circulating microRNAs in vivo following administration of dexamethasone and adrenocorticotropin. Int. J. Endocrinol. 2015, 589230 (2015). https://doi.org/10.1155/2015/589230 CrossRefPubMedPubMedCentral

17.

W. Arlt, M. Biehl, A.E. Taylor, S. Hahner, R. Libé, B.A. Hughes, P. Schneider, D.J. Smith, H. Stiekema, N. Krone, E. Porfiri, G. Opocher, J. Bertherat, F. Mantero, B. Allolio, M. Terzolo, P. Nightingale, C.H. Shackleton, X. Bertagna, M. Fassnacht, P.M. Stewart, Urinesteroid metabolomics as a biomarker tool for detecting malignancy in adrenal tumors. J. Clin. Endocrinol. Metab. 96, 3775–3784 (2011). https://doi.org/10.1210/jc.2011-1565 CrossRefPubMedPubMedCentral

18.

I. Bancos, W. Arlt, Diagnosis of a malignant adrenal mass: the role of urinary steroid metabolite profiling. Curr. Opin. Endocrinol. Diabetes Obes. 24, 200–207 (2017). https://doi.org/10.1097/MED.0000000000000333 CrossRefPubMed

19.

M. Fassnacht, S. Johanssen, M. Quinkler, P. Bucsky, H.S. Willenberg, F. Beuschlein, M. Terzolo, H.H. Mueller, S. Hahner, B. Allolio German Adrenocortical Carcinoma Registry Group, European Network for the Study of Adrenal Tumors Limited prognostic value of the 2004 International Union Against Cancer staging classification for adrenocortical carcinoma: proposal for a Revised TNM Classification. Cancer 115, 243–250 (2009).https://doi.org/10.1002/cncr.24030 CrossRefPubMed

20.

H. Schwarzenbach, N. Nishida, G.A. Calin, K. Pantel, Clinicalrelevance of circulating cell-free microRNAs in cancer. Nat. Rev. Clin. Oncol. 11, 145–156 (2014). https://doi.org/10.1038/nrclinonc.2014.5 CrossRefPubMed

21.

P.S. Mitchell, R.K. Parkin, E.M. Kroh, B.R. Fritz, S.K. Wyman, E.L. Pogosova-Agadjanyan, A. Peterson, J. Noteboom, K.C. O’Briant, A. Allen, D.W. Lin, N. Urban, C.W. Drescher, B.S. Knudsen, D.L. Stirewalt, R. Gentleman, R.L. Vessella, P.S. Nelson, D.B. Martin, M. Tewari, Circulating microRNAs as stable blood-based markers for cancer detection. Proc. Natl. Acad. Sci. USA 105, 10513–10518 (2008). https://doi.org/10.1073/pnas.0804549105 CrossRefPubMedPubMedCentral

22.

E. Duregon, I. Rapa, A. Votta, J. Giorcelli, F. Daffara, M. Terzolo, G.V. Scagliotti, M. Volante, M. Papotti, MicroRNA expression patterns in adrenocortical carcinoma variants and clinical pathologic correlations. Hum. Pathol. 45, 1555–1562 (2014). https://doi.org/10.1016/j.humpath.2014.04.005 CrossRefPubMed

23.

C. Devlin, S. Greco, F. Martelli, M. Ivan, miR-210: More than a silent player in hypoxia. IUBMB Life 63, 94–100 (2011). https://doi.org/10.1002/iub.42710.1002/iub.427 PubMedPubMedCentral

24.

W.J. Chen, K. Yin, G.J. Zhao, Y.C. Fu, C.K. Tang, The magic and mystery of microRNA-27 in atherosclerosis. Atherosclerosis 222, 314–323 (2012). https://doi.org/10.1016/j.atherosclerosis.2012.01.020 CrossRefPubMed

25.

K. Kaur, A.K. Pandey, S. Srivastava, A.K. Srivastava, M. Datta, Comprehensive miRNome and in silico analyses identify the Wnt signaling pathway to be altered in the diabetic liver. Mol. Biosyst. 7, 3234 (2011). https://doi.org/10.1039/c1mb05041a CrossRefPubMed

26.

Y. Li, C. Qiu, J. Tu, B. Geng, J. Yang, T. Jiang, Q. Cui, HMDDv2.0: a database for experimentally supported human microRNA and disease associations. Nucleic Acids Res. 42, D1070–D1074 (2014). https://doi.org/10.1093/nar/gkt1023. Database issueCrossRefPubMed

27.

N.H. Heegaard, A.J. Schetter, J.A. Welsh, M. Yoneda, E.D. Bowman, C.C. Harris, Circulating micro-RNA expression profiles in early stage nonsmall cell lung cancer. Int. J. Cancer 130, 1378–1386 (2012). https://doi.org/10.1002/ijc.26153 CrossRefPubMed

28.

J. Wang, Y. Li, M. Ding, H. Zhang, X. Xu, J. Tang, Molecular mechanisms and clinical applications of miR-22 in regulating malignant progression in human cancer (Review). Int. J. Oncol. 50, 345–355 (2017). https://doi.org/10.3892/ijo.2016.3811 CrossRefPubMed

29.

Q.L. Lv, H. Du, Y.L. Liu, Y.T. Huang, G.H. Wang, X. Zhang, S.H. Chen, H.H. Zhou, Low expression of microRNA-320b correlates with tumorigenesis and unfavorable prognosis in glioma. Oncol. Rep. 38, 959–966 (2017). https://doi.org/10.3892/or.2017.5762 CrossRefPubMed

Titel: Analysis of circulating extracellular vesicle-associated microRNAs in cortisol-producing adrenocortical tumors
verfasst von: Pál Perge
Ábel Decmann
Raffaele Pezzani
Irina Bancos
Ambrogio Fassina
Michaela Luconi
Letizia Canu
Miklós Tóth
Marco Boscaro
Attila Patócs
Peter Igaz
Publikationsdatum: 03.01.2018
Verlag: Springer US
Erschienen in: Endocrine / Ausgabe 2/2018
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-017-1506-z

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren.

Wo hapert es noch bei der Umsetzung der POMGAT-Leitlinie?

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Das Risiko für Vorhofflimmern in der Bevölkerung steigt

02.05.2024 Vorhofflimmern Nachrichten

Das Risiko, im Lauf des Lebens an Vorhofflimmern zu erkranken, ist in den vergangenen 20 Jahren gestiegen: Laut dänischen Zahlen wird es drei von zehn Personen treffen. Das hat Folgen weit über die Schlaganfallgefährdung hinaus.

VHF-Ablation nützt wohl nur bei reduzierter Auswurfleistung

02.05.2024 Ablationstherapie Nachrichten

Ob die Katheterablation von Vorhofflimmern bei Patienten mit Herzinsuffizienz die Komplikationsraten senkt, scheint davon abzuhängen, ob die Auswurfleistung erhalten ist oder nicht. Das legen die Ergebnisse einer Metaanalyse nahe.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Chronische Unterbauch- und Viszeralschmerzen in der Praxis managen"

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2018

Skeletal fragility induced by overtreatment of adrenal insufficiency

Effects of growth hormone on thyroid function are mediated by type 2 iodothyronine deiodinase in humans

Parathyroid hormone in surgery-induced weight loss: no glucometabolic effects but potential adaptive response to skeletal loading

Clinical profile of juvenile primary hyperparathyroidism: a prospective study

The relationship among serum lipocalin 2, bone turnover markers, and bone mineral density in outpatient women