ECE2017 Guided Posters Adrenal 1 (10 abstracts)
Clinical and translational relevance of circulating miR483 in adrenocortical cancer
Letizia Canu 1 , Francesca Salvianti 1 , Giada Poli 1 , Roberta Armignacco 1 , Giulia Cantini 1 , Alessandra Di Franco 1 , Stefania Gelmini 1 , Tonino Ercolino 1 , Massimo Terzolo 2 , Gabriella Nesi 1 , Pamela Pinzani 1 , Massimo Mannelli 1 & Michaela Luconi 1
1University of Florence, Florence, Italy; 2University of Turin, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.
Adrenocortical cancer (ACC) is a rare aggressive malignancy, with poor prognosis when metastaic at diagnosis. Recent ACC pan-genomics analysis contributed to redefine the risk groups on molecular bases, including tumor micro RNA (miR), which can be detectable not only in the primary lesion but also in the bloodstream.
We develop a quantitative real-time assay for the measurement of absolute levels in plasma samples of miR483 and its mature miR483-5p form. miR483/miR483-5p levels were evaluated in plasma samples of 27 patients with ACC before surgery and at follow up, and in an independent validation cohort of 21 metastatic ACC.
Statistically significant difference in miR483-5p and miR483 levels of pre-surgery and post-surgery samples was found between low (stage 1/2) and high (stage 3/4) risk groups. Moreover the mean levels of both miRs were significantly higher in plasma of patients belonging to the high stage risk group compared to subjects with the benign form (ACA) and healthy subjects. ROC curves analysis of miR483–5p levels resulted in predicting the risk stage (accuracy 0.917±0.084). The best ROC cut-off value for miR483-5p (0.221 ng/ml) significantly predicted overall and recurrence-free survival. miR483-5p was the only variable that significantly predicts recurrence, but not overall survival, in a multivariate Cox analysis (HR 16.2, 95%CV[1.39–188.6, P<0.026]). In addition, miR483 and 483-5p levels significantly correlated with the number of circulating tumor cells in the same blood samples, independently of the timing of sampling. Analysis of an independent cohort of metastatic ACC (n=21) revealed that miR483 negatively correlated with mitotane levels.
In conclusion, we demonstrated that miR483 and miR483-5p absolute plasma levels in ACC patients are powerful molecular markers that may help to follow patients after surgery and chemotherapy, and contribute to better classify and predict tumor evolution.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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