In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 3050-3050
Abstract:
Barrett's Mucosa (BM) is a metaplastic replacement of the native esophageal (squamous) epithelium (ESq) by columnar-intestinalized mucosa. BM is the main risk factor for Barrett's adenocarcinoma (BAc). MicroRNAs (miRNAs) are a class of small non-coding RNAs that control gene expression by targeting mRNAs; miRNAs deregulation has been associated with Barrett's oncogenesis. To explore the hypothesis that a specific miRNAs signature is associated with BM (and its associated cancer risk) a miRNA microarray analysis (OSU-CCC version 4.0; Ohio State University) compared ESq versus all the spectrum of the phenotypic lesions of the Barrett's carcinogenesis. Specimens were collected at Department of Pathology of Padova University from 14 patients undergone esophagectomy for BAc or High-grade non-invasive neoplasia (HG-NiN). Tissues samples for the microarray study included: ESq= 14 samples; BM= 14; Low-grade non-invasive neoplasia (LG-NiN)= 7; HG-NiN= 5; BAc= 11. The miRNA-profiling study consistently disclosed increased expression of 6 miRNAs (hsa-miR-215, hsa-miR-560, hsa-miR-615-3p, hsa-miR-192, hsa-miR-326, hsa-miR-147), and decreased expression of 7 others (hsa-miR-100, hsa-miR-23a, hsa-miR-605, hsa-miR-99a, hsa-miR-205, hsa-let-7c, hsa-miR-203). Microarray results were further validated by qRT-PCR, using a different series of 10 consecutive BAc cases (Esq= 10 samples; BM= 6 samples; BAc= 10 samples). Interestingly, some of the miRNAs found deregulated in this series are already known as suitable markers of cancer progression in other models of epithelial oncogenesis (i.e.: hsa-let-7c, hsa-miR-192, hsa-miR-203, hsa-miR-205, hsa-miR-215). The results achieved by the miRNA profiling study were further validated by the immunohistochemical (IHC) analysis on a well-defined miRNA gene target (HMGA2 [hsa-let-7c]). The IHC expression of the protein product was consistent with the corresponding miRNA's deregulation. In fact, HMGA2 IHC expression was up-regulated in HG-NiN and BAc. The achieved results confirm that specific miRNAs are involved in BM carcinogenesis and that they may represent a novel diagnostic/prognostic tool in the characterization of BAc gene targets. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3050.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM10-3050
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2010
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
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