There is a critical need to identify molecular markers that can reliably aid in stratifying esophageal adenocarcinoma (EAC) risk in patients with Barrett's esophagus. MicroRNAs (miRNA/miR) are one such class of biomolecules. In the present cross-sectional study, we characterized miRNA alterations in progressive stages of neoplastic development, i.e., metaplasia-dysplasia-adenocarcinoma, with an aim to identify candidate miRNAs potentially associated with progression. Using next generation sequencing (NGS) as an agnostic discovery platform, followed by quantitative real-time PCR (qPCR) validation in a total of 20 EACs, we identified 26 miRNAs that are highly and frequently deregulated in EACs (≥ 4-fold in >50% of cases) when compared to paired normal esophageal squamous (nSQ) tissue. We then assessed the 26 EAC-derived miRNAs in laser microdissected biopsy pairs of Barrett's metaplasia (BM)/nSQ (n = 15), and high-grade dysplasia (HGD)/nSQ (n = 14) by qPCR, to map the timing of deregulation during progression from BM to HGD and to EAC. We found that 23 of the 26 candidate miRNAs were deregulated at the earliest step, BM, and therefore noninformative as molecular markers of progression. Two miRNAs, miR-31 and -31*, however, showed frequent downregulation only in HGD and EAC cases suggesting association with transition from BM to HGD. A third miRNA, miR-375, showed marked downregulation exclusively in EACs and in none of the BM or HGD lesions, suggesting its association with progression to invasive carcinoma. Taken together, we propose miR-31 and -375 as novel candidate microRNAs specifically associated with early- and late-stage malignant progression, respectively, in Barrett's esophagus.
"However, very few studies have been conducted to identify miRNAs as prognostic biomarkers for the progression of Barrett's esophagus to adenocarcinoma . Although several cross-sectional studies using comprehensive array analysis have been reported (Feber et al., 2008; Kan et al., 2009; Yang et al., 2009; Fassan et al., 2011; Leidner et al., 2012; Wu et al., 2013), their results have proved controversial . They compared the expression of miRNAs across different types of histological specimens such as Barrett's esophagus, low-grade dysplasia, high-grade dysplasia , and esophageal adenocarcinoma, and reported that a substantial number of miRNAs show differential expression in esophageal tissues (Sakai et al., 2013). "
"Down Esophageal adenocarcinoma Late-stage progression in barrett's esophagus Tumor tissue  Down Squamous cell cervical cancer Prognosis Tumor tissue  Up Prostate cancer Diagnosis and cancer pro- gression Tumor tissue, serum   let-7 family Up (let-7a) Breast cancer Diagnosis Blood  Down Lung cancer Diagnosis, prognosis, and tumor classification Tumor tissue    Down (let-7a) Gastric cancer Diagnosis Plasma  Up Gastric cancer Prognosis (stage- independent) Tumor tissue  "
[Show abstract][Hide abstract] ABSTRACT: MicroRNAs (miRNAs) are attractive, short, non-coding RNAs widely studied for their fundamental roles in tissue homeostasis, cell proliferation, and dysregulation in cancer. A vast majority of investigations and technical improvements have focused on miRNAs' tumor-specific expression patterns, which provide novel molecular biomarkers for cancer detection and targeted therapies. In this review, we focus on recent achievements in biomarker validation and potential for cancer treatment, with special trend in non-invasive strategies to evaluate miRNAs, especially for diagnostic and prognostic applications. We further include a large compilation of PubMed data regarding microRNAs reported as diagnostic or prognostic cancer biomarkers in at least three studies.
[Show abstract][Hide abstract] ABSTRACT: Esophageal cancer (EC) is one of the most common malignant tumors worldwide. EC is usually diagnosed at a locally advanced stage or at a stage with involvement of lymph nodes. Despite aggressive treatment, the overall five-year survival rate remains poor. microRNAs (miRNAs) are small, non-coding endogenous RNAs that negatively regulate gene expression at the post-transcriptional and/or translational level. Accumulating evidence suggests that the deregulation of miRNAs not only results in cancer progression, but also directly promotes tumor initiation. Previous studies found that miRNAs are frequently deregulated in EC, indicating that miRNAs are important in tumorigenesis. In this review, we summarize therecently recognized miRNA expression and its impact on the biology of EC and the potential applications for EC.
Molecular Medicine Reports 06/2012; 6(3):459-65. DOI:10.3892/mmr.2012.975 · 1.55 Impact Factor
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