P105 MIRNA483-3P AND MIRNA221 DYSREGULATION AND CORRELATION WITH SURVIVAL IN ESOPHAGEAL ADENOCARCINOMA (EAC)

Abstract Aim Our study aimed to characterize miR-221 and 483-3p dysregulation and to correlate their expression with clinical outcomes in patients submitted in first instance to surgical therapy (naïve patients) for esophageal adenocarcinoma (EAC). Background & Methods MicroRNA (miRNAs) are smal...

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Published in:Diseases of the esophagus 2019-11, Vol.32 (Supplement_2)
Main Authors: Isidori, F, Bozzarelli, I, Lugaresi, M, Malvi, D, Mastracci, L, Hoefnagel, S J M, Räsänen, J, Söderström, H, Raulli, G, D’Errico, A, Fiocca, R, Seri, M, Krishnadath, K K, Bonora, E, Mattioli, S
Format: Article
Language:English
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Summary:Abstract Aim Our study aimed to characterize miR-221 and 483-3p dysregulation and to correlate their expression with clinical outcomes in patients submitted in first instance to surgical therapy (naïve patients) for esophageal adenocarcinoma (EAC). Background & Methods MicroRNA (miRNAs) are small, noncoding RNAs that play important roles in several biological processes by fine-tuning gene expression1. In a cohort of well-characterized EAC, we analyzed the expression of miRNAs. RNA was extracted from formalin-embedded (FFPE) surgical specimens of normal gastric tissues and EACs, classified according to BIM/GIM classification (BIM=Barrett’s intestinal metaplasia, GIM=Gastric intestinal metaplasia): 43 BIM-/GIM-, 32 BIM+/GIM-, 2 BIM+/GIM+, 9 BIM-/GIM+). Expression of 754 human miRNAs was profiled in 8 cases with TaqMan MicroRNA Array card A1.1/B3.0. miR-221 and 483-3p validation was performed with single TaqMan probes on all 85 FFPE samples. miR-221 and miR-483-3p were also analyzed in a cohort of 39 fresh-frozen biopsies (29 EAC and 10 normal esophageal tissues). In 3 EAC cell-lines (OE-19, OE-33, FLO-1)2 we tested the expression of miR-221 and miR-483-3p3 and of two major targets (PTEN and SMAD4, respectively). Correlations between miRNAs and clinical outcomes were calculated using Kruskal-Wallis, Mann-Whitney, t-Student’s and Kaplan-Meier tests. Results miR-221 and 483-3p resulted upregulated from the MicroRNA Array card analysis. This increase was confirmed in two independent cohorts (FFPE-cohort: miR-483-3p p=0.0065; fresh-frozen-cohort: miR-483-3p p
ISSN:1120-8694
1442-2050
DOI:10.1093/dote/doz092.105