Abstract 1865: Circulating microRNA expression profile: miR-1246 and miR-185 profile as a novel diagnostic biomarker for melanoma

Abstract

Abstract Melanoma is the leading cause of fatal skin cancer, and in the past few decades, there has been an increase in the incidence of and mortality from metastatic melanoma. The conventional pathological assessment of the tumor is to date the better pronostic factor. Non invasive biomarkers are needed to assess the aggressivity of the tumor. Many serum biomarkers were assessed in melanoma, but due their low sensitivity and reduced specificity, their clinical significance remains a matter of debate. MicroRNAs (miRNAs) are non small coding RNAs with regulatroy roles on gene expression which are involved in a broad spectrum of physiological and pathological processes. The miRNAs have been described to circulate in highly stable, cell-free forms in blood and to have potential of useful non-invasive biomarkers for diagnosis, prognosis and prediction of therapeutic response in cancer. Initially we performed a miRNA array (576 human miRNAs) using plasma samples from metastatic melanoma patients and healthy controls. 25 miRNAs upregulated were selected for further analysis along with 21 miRNAs described in litterature to be dysregulated in melanoma cells and tissues. We screened expression of these miRNAs in plasma samples of a training cohort (16 controls and 29 metastatic melanoma patients) using the BioMark™ 96.96 Dynamic Array (Fluidigm Corporation) for real-time qPCR was used to simultaneously test up to 96 samples against 96 microRNAs primers in a single experiment at nanoliter scale. Then miRNAs of interest were then validated in an independent cohort of 43 controls and 31 patients. After these processes, 5 miRNAs (Let-7b, miR-20a, miR-185, miR-338 and mir-1246) displayed significantly different expression levels in melanoma compared with controls. These miRNas had high sensitivity and specificity but the combination of miR-185 and miR-1246 was extremely more sensitive (90.5%) and specific (89.1%) than each individual miRNA to accurately discern patients and healthy donors. Moreover among these miRNAs, we observed that miR-185 expression is associated with a significant increase in survival and may have a protective effect, with an adjusted hazard ratio of 0.43, showing that miR-185 level could serve as an important marker for predicting the survival rate independently of other clinical and pathological factors. All our results showed that co-detection of miR-185 and miR-1246 profile in the plasma may be used as a biomarker for monitoring of patients with high recurrence-risk melanoma. We propose that co-detection of miR-185 and miR-1246 may allow early detection of disease recurrence or identification of a patient subpopulation requiring adjuvant therapies Note: This abstract was not presented at the meeting. Citation Format: Virginie Armand-Labit, Nicolas Meyer, Anne Casanova, Stephane Verdun, Marie Bruillard, Gilles Favre, Anne Pradines. Circulating microRNA expression profile: miR-1246 and miR-185 profile as a novel diagnostic biomarker for melanoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1865. doi:10.1158/1538-7445.AM2014-1865