Analysis of circulating microRNAs in adrenocortical tumors

Abstract

Differential diagnosis of adrenocortical adenoma (ACA) and carcinoma is of pivotal clinical relevance, as the prognosis and clinical management of benign and malignant adrenocortical tumors (ACTs) is entirely different. Circulating microRNAs (miRNAs) are promising biomarker candidates of malignancy in several tumors; however, there are still numerous technical problems associated with their analysis. The objective of our study was to investigate circulating miRNAs in ACTs and to evaluate their potential applicability as biomarkers of malignancy. We have also addressed technical questions including the choice of profiling and reference gene used. A total of 25 preoperative plasma samples obtained from patients with ACAs and carcinomas were studied by microarray and quantitative real-time PCR. None of the three miRNAs (hsa-miR-192, hsa-mir-197 and hsa-miR-1281) found as differentially expressed in plasma samples in our microarray screening could be validated by quantitative real-time PCR. In contrast, of the selected eight miRNAs reported in the literature as differentially expressed in ACT tissues, five (hsa-miR-100, hsa-miR-181b, hsa-miR-184, hsa-miR-210 and hsamiR-483-5p) showed a statistically significant overexpression in adrenocortical cancer vs adenoma when normalized on hsa-miR-16 as a reference gene. Receiver operator characteristic analysis of data revealed that the combination of dCT hsa-miR-210 -dCT hsa-miR-181b and dCT hsa-miR-100 /dCT hsa-miR-181b showed the highest diagnostic accuracy (area under curve 0.87 and 0.85, respectively). In conclusion, we have found significant differences in expression of circulating miRNAs between ACAs and carcinomas, but their diagnostic accuracy is not yet high enough for clinical application. Further studies on larger cohorts of patients are needed to assess the diagnostic and prognostic potential application of circulating miRNA markers.

The next step: mechanisms driving adrenocortical carcinoma metastasis

“…2). This is a novel and minimally invasive technique developed for solid tumors and recently also applied to ACC (Chabre et al 2013, Szabó et al 2014, Creemers et al 2017, Batth et al 2017, Bardelli & Pantel 2017 to identify potential markers to assess malignancy in ACC, even if the predictive power needs to be confirmed on larger cohorts of patients. In addition to its diagnostic/ prognostic value, the liquid biopsy represents a unique tool that can provide informative material to be analyzed and compared to the primary lesion for longitudinal surveillance of clonal evolution and progression of the tumor, also in response to anticancer treatments.…”

“…Among the different circulating miRNA profiles characterized in ACC (Szabó et al 2014), miR-483-5p is the recurrent one in almost all the studies and the most suggestive one as it maps in the second intron of the IGF2 gene, whose hyperexpression is a recurrent tract of aggressive ACC (Giordano et al 2009). Indeed, miR-483-5p has been demonstrated to be overexpressed both in the primary tumor (Soon et al 2009, Patterson et al 2011, Duregon et al 2014b) and the bloodstream (Chabre et al 2013, Patel et al 2013, Szabó et al 2014).…”

“…Indeed, miR-483-5p has been demonstrated to be overexpressed both in the primary tumor (Soon et al 2009, Patterson et al 2011, Duregon et al 2014b) and the bloodstream (Chabre et al 2013, Patel et al 2013, Szabó et al 2014). Chabre and coworkers showed that high circulating serum levels of miR-483-5p and low circulating levels of miR-195 in 21 ACCs stratified into non-aggressive and aggressive cancers were associated with both shorter DFS and OS (Chabre et al 2013).…”

Keringő mikroRNS-ek az endokrin daganatok diagnosztikájában

“…Kutatócsoportunk is vizsgálta korábban a mellékvesekéreg-carcinoma keringő mikro-RNS-mintázatát. Ugyancsak mellékvesekéreg-adenomá-val összehasonlítva a miR-100, a miR-181b, a miR-184, a miR-210, illetve a miR-483-5p felülexpresszálódása volt szignifikáns [31]. Egy másik tanulmányunkban bemutattuk, hogy a miR-483-5p kifejeződését nem befolyásolja dexamethason vagy adrenokortikotropin adása, ami megerősíti, hogy az ACC preoperatív diagnosztiká-jában potenciális szerepe lehet [32].…”

“…Az újonnan felfedezett keringő mikroRNS-ek száma fokozatosan közelít a szövetekben leírt mikroRNS-ek számához, és egyre több eredményt közölnek a keringő mikroRNS-ek diagnosztikus jelentőségéről daganatos betegségekben. Az eredmények között azonban számos eltérés figyelhető meg, ugyanazon daganatok esetében különböző munkacsoportok gyakran teljesen más mikroRNS-mintázatokat írnak le, amiben a mintaválasztás, mikroRNS-analízis és normalizálás különbségei is szerepet játszanak [31], valamint a társbetegségek is fontosak lehetnek. Az endokrin daganatokra vonatkozóan viszonylag kevés adat áll rendelkezésünkre, bár a változás egy év alatt is figyelemreméltó [47].…”