Oncotarget

Research Papers:

New insights in the clinical and translational relevance of miR483-5p in adrenocortical cancer

Francesca Salvianti, Letizia Canu, Giada Poli, Roberta Armignacco, Cristian Scatena, Giulia Cantini, Alessandra Di Franco, Stefania Gelmini, Tonino Ercolino, Mario Pazzagli, Gabriella Nesi, Massimo Mannelli, Pamela Pinzani and Michaela Luconi _

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Oncotarget. 2017; 8:65525-65533. https://doi.org/10.18632/oncotarget.19118

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Abstract

Francesca Salvianti1,*, Letizia Canu1,*, Giada Poli1, Roberta Armignacco1, Cristian Scatena2, Giulia Cantini1, Alessandra Di Franco1, Stefania Gelmini1, Tonino Ercolino1, Mario Pazzagli1, Gabriella Nesi3, Massimo Mannelli1, Pamela Pinzani1,* and Michaela Luconi1,*

1Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy

2Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy

3Department of Surgery and Translational Medicine, University of Florence, Florence, Italy

*These authors have equally contributed to the work

Correspondence to:

Michaela Luconi, email: [email protected]

Keywords: adrenal carcinoma, miRNA, liquid biopsy, rare tumor, quantitative real time RT-PCR

Received: February 27, 2017    Accepted: April 19, 2017    Published: July 10, 2017

ABSTRACT

Adrenocortical cancer (ACC) is a rare aggressive malignancy. Recent ACC integrated genomics analysis contributed to redefine the risk groups on molecular basis, including tumor microRNAs (miRs), detectable also in the bloodstream. We developed a quantitative real-time (RT) assay for the measurement of miR483 and miR483-5p absolute levels in plasma samples. miR483/miR483-5p levels were evaluated in plasma samples of 27 patients with ACC before surgery and at follow-up.

Statistically significant differences in miR483-5p and miR483 levels were found between stage 1/2 and stage 3/4 ACCs in pre-surgery and post-surgery samples. ROC curve analysis of miR483–5p levels gave a prediction of the clinical stage (accuracy 0.917±0.084), with the best cut-off value of 0.221 ng/ml, prognosticating overall and recurrence-free survival. In a multivariate Cox analysis (HR 16.2, 95%CI[1.39-188.6, P<0.026]), miR483-5p was the only variable that significantly predicted recurrence, but not overall survival. In addition, miR483 and miR483-5p levels correlated with the number of circulating tumor cells (CTCs) detected in the same blood samples, independently of the timing of sampling. In conclusion, we demonstrated that miR483-5p absolute plasma levels in ACC patients are powerful molecular markers that may help in the follow-up of patients after surgery and chemotherapy, and contribute to more accurately classify and predict tumor progression.


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