LB-FP-1 Serum miR-195 and miR-483-5p are predictive of recurrence risk in adrenocortical cancer patients

Program: Late-Breaking Abstracts
Session: SAT-LB-Late-Breaking Poster Session 1
Bench to Bedside
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-LB-01
Nadia Cherradi*1, Rossella Libe2, Guillaume Assie3, Olivia Barreau3, Jerome Yves Bertherat4, Xavier Y Bertagna4, Jean-Jacques Feige1 and Olivier Chabre5
1INSERM U1036, Grenoble, France, 2Inserm U1016, CNRS UMR 8104, Institut Cochin, Paris, France, 3Inserm U1016, CNRS UMR 8104, Institut Cochin, Paris Descartes University, Paris, 4Hopital Cochin, Paris, France, 5University Hospital Grenoble, Grenoble, France
Adrenocortical carcinoma (ACC) is a rare cancer with poor prognosis. Local and distant recurrences occur in a subset of tumors classified as “aggressive” ACC (aACC), as opposed to “non-aggressive” ACC (naACC). In this study, we investigated whether tissue and serum microRNAs (miRNAs) are predictive of ACC aggressiveness. MiRNA expression profiles were determined using microarrays in a test series of adrenocortical adenomas (ACA), naACC and aACC. Eight miRNAs were selected for further validation by quantitative RT-PCR (validation cohort: 10 ACA, 9 naACC, 9 aACC, and 3 normal adrenocortical tissues). Quantification of selected miRNAs was performed in serum samples from 56 subjects (19 healthy controls, 14 ACA, 9 naACC and 14 aACC patients). MiR-195 levels were significantly decreased in both tumor and serum samples of ACC patients relative to ACA patients and healthy controls. MiR-139-5p and miR-376a levels were significantly increased in aACC compared to naACC patients in tumor samples only. Very interestingly, miR-483-5p, a miRNA which is located within the second intron of insulin-like growth factor Igf2 gene, was dramatically increased in 80 % of ACC compared to ACA tumor samples. In addition, serum miR-483-5p was detected only in aACC patients, suggesting that its release in the bloodstream is related to advanced disease. Receiver operating characteristic (ROC) analyses indicated that serum miR-195 and miR-483-5p had a high diagnostic value for ACC and aACC patients, respectively. Kaplan-Meier analyses revealed that low circulating levels of miR-195 and high circulating levels of miR-483-5p were associated with poor prognosis (p=0.0314 and p=0.0003, respectively) and short recurrence-free survival of ACC patients (p=0.0097 and p=0.0004, respectively). In conclusion, the present study reports for the first time that circulating miR-195 and miR-483-5p are promising non-invasive biomarkers with a highly specific prognostic value for the clinical outcome of ACC patients.

Nothing to Disclose: NC, RL, GA, OB, JYB, XYB, JJF, OC

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: This work was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM, U1036), the Commissariat à l’Energie Atomique (iRTSV/BCI), the Recherche Translationnelle DHOS/INCA 2009 [RTD09024], the Conny-Maeva Foundation and the « Ligue Départementale Contre le Cancer » (Comité de la Loire).
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