Reema Mallick1, Santosh K Patnaik2, Sachin Wani3, Ajay Bansal4,5. 1. Department of Surgery, University of Minnesota, Minneapolis, MN, USA. 2. Department of Thoracic Surgery, Roswell Park Cancer Institute, Buffalo, NY, USA. 3. Department of Gastroenterology, University of Colorado, Aurora, CO, USA. 4. Division of Gastroenterology and Hepatology, Veterans Affairs Medical Center, Kansas City, MO, USA. abansal@kumc.edu. 5. Department of Gastroenterology, University of Kansas School of Medicine, Kansas City, KS, USA. abansal@kumc.edu.
Abstract
BACKGROUND: Esophageal epithelial microRNAs may be used to diagnose Barrett's esophagus (BE) and possibly monitor its progression to esophageal adenocarcinoma (EAC). AIMS: We reviewed studies that have investigated this to identify microRNAs with high biomarker potential for screening and disease monitoring in BE. METHODS: PubMed and EMBASE databases were searched for studies that quantified esophageal epithelial microRNAs. Publications reporting microRNA comparisons of normal, non-dysplastic BE, BE with high-grade dysplasia (HGD), and EAC tissues using both unbiased discovery and independent validation phases were reviewed. RESULTS: Eleven studies on microRNA expression differences between normal epithelium and non-dysplastic BE (seven studies), HGD (4) or EAC (7), or between non-dysplastic BE and HGD (3) or EAC (6) were identified, and the findings of their validation phase were analyzed. Increased miR-192, -194, and -215, and reduced miR-203 and -205 expression in BE compared to normal was noticed by all 4-6 of the seven studies that examined these microRNAs. In heterogeneity tests of the reported fold-change values, the I (2) statistics were 7.9-17.1 % (all P < 0.05). Elevated miR-192, -194, and -215, and diminished miR-203 and -205 levels were also noted for comparisons of HGD or EAC against normal. In contrast, a consistent microRNA expression difference was absent for the comparisons of HGD or EAC against BE. CONCLUSIONS: MicroRNAs miR-192, -194, -203, -205, and -215 are promising tissue biomarkers for diagnosing BE. Cross-sectional data suggest that microRNAs may have a limited role in separating BE from HGD/EAC epithelia but need further testing in longitudinal follow-up studies.
BACKGROUND: Esophageal epithelial microRNAs may be used to diagnose Barrett's esophagus (BE) and possibly monitor its progression to esophageal adenocarcinoma (EAC). AIMS: We reviewed studies that have investigated this to identify microRNAs with high biomarker potential for screening and disease monitoring in BE. METHODS: PubMed and EMBASE databases were searched for studies that quantified esophageal epithelial microRNAs. Publications reporting microRNA comparisons of normal, non-dysplastic BE, BE with high-grade dysplasia (HGD), and EAC tissues using both unbiased discovery and independent validation phases were reviewed. RESULTS: Eleven studies on microRNA expression differences between normal epithelium and non-dysplastic BE (seven studies), HGD (4) or EAC (7), or between non-dysplastic BE and HGD (3) or EAC (6) were identified, and the findings of their validation phase were analyzed. Increased miR-192, -194, and -215, and reduced miR-203 and -205 expression in BE compared to normal was noticed by all 4-6 of the seven studies that examined these microRNAs. In heterogeneity tests of the reported fold-change values, the I (2) statistics were 7.9-17.1 % (all P < 0.05). Elevated miR-192, -194, and -215, and diminished miR-203 and -205 levels were also noted for comparisons of HGD or EAC against normal. In contrast, a consistent microRNA expression difference was absent for the comparisons of HGD or EAC against BE. CONCLUSIONS: MicroRNAs miR-192, -194, -203, -205, and -215 are promising tissue biomarkers for diagnosing BE. Cross-sectional data suggest that microRNAs may have a limited role in separating BE from HGD/EAC epithelia but need further testing in longitudinal follow-up studies.
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