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.
Highlights
Adrenocortical carcinoma (ACC) is a rare but often aggressive tumor, with dismal prognosis and limited therapeutic options
The liquid biopsy can provide important information on circulating tumor cells (CTCs) detached from the tumor mass, as well as on the molecular markers released by the tumor, such as circulating miR and free DNA
The sensitivity of the miR quantification technique used was low, as miR483-5p in serum samples of non-aggressive tumors was under the detection limit of the method and no cut-off value derived from Receiver operating characteristic (ROC) curves and used for recurrence or survival analysis was given
Summary
Adrenocortical carcinoma (ACC) is a rare but often aggressive tumor, with dismal prognosis and limited therapeutic options. In addition to the profiles derived from the analysis of the characteristics of the primary tumor mass, information provided by the liquid biopsy components, i.e. miRNA (miR), free circulating DNA, and circulating tumor cells (CTCs), can better characterize tumors at a molecular level [4]. The liquid biopsy is a non-invasive test on blood samples, and provides biological material to monitor www.impactjournals.com/oncotarget the tumor progression and response to therapies. Integration of this molecular information enables the identification of subgroups of malignant tumors with distinct molecular alterations and clinical outcomes, enabling the possibility of future personalized therapeutic approaches [5]. We measured miR483 and miR483-5p absolute plasma levels of a cohort of 27 ACC patients before and after surgery, uncovering correlations with disease stage and predictive values for the -5p variant
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