Barrett’s esophagus is a condition in which the tissue lining the esophagus, the muscular tube that carries food and liquids from the mouth to the stomach, is replaced by tissue that is similar to the intestinal lining. In this process which is called intestinal metaplasia, normal cells that line the esophagus, called squamous cells, turn into cells not usually found in humans, called specialized columnar cells.

Barrett’s esophagus is a precursor lesion of esophageal adenocarcinoma. The progression of the disease follows sequential stages. However, the low progression rate and the inadequacy and subjective interpretation of histologic grading in predicting Barrett’s esophagus progression call for more objective biomarkers that can improve risk prediction.

microRNA expression
A series of microRNA expression signatures that may help to define progression of the precancerous condition Barrett?s esophagus into esophageal adenocarcinoma was reported recently in Cancer Prevention Research, a journal of the American Association for Cancer Research.

Fastest-rising incidence
?Once a rare cancer representing only 5% of all esophageal cancers in the United States, esophageal adenocarcinoma is the cancer with the fastest-rising incidence ? six-fold increase in the past three decades ? and currently comprises more than 80% of all new esophageal cancer cases in this country,? said Xifeng Wu, M.D., chair of the Department of Epidemiology, Division of Cancer Prevention and Population Sciences at The University of Texas MD Anderson Cancer Center, in Houston. ?To reduce the mortality of esophageal adenocarcinoma, the best hope in the near term is to detect it at its early stage, or even better, to prevent the progression of esophageal adenocarcinoma from its premalignant lesion, which is called Barrett?s esophagus.?

Wu and colleagues evaluated microRNAs, which are a class of small ribonucleic acids in cells capable of regulating a large number of genes. Research has shown that aberrant expression of microRNAs is involved in cancer development. The researchers compared hundreds of microRNAs in normal esophageal epithelia and in Barrett?s esophagus and esophageal adenocarcinoma tissues of different histological grades with distinct progression risks. They identified a number of differentially expressed microRNAs at each histological stage.

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Remarkably similar Tissues
?The expression of microRNAs in Barrett?s esophagus and esophageal adenocarcinoma tissues was remarkably similar, indicating that the microRNA aberrations were very early events in the development of Barrett?s esophagus,? Wu said. ?These aberrations in microRNA expression may drive other late events that ultimately lead to carcinoma formation.?

The researchers also identified a small number of microRNAs that were significantly different between Barrett?s esophagus and esophageal adenocarcinoma. Specifically, downregulation of the microRNA miR-375 and upregulation of five microRNAs of the miR-17-92 and homologue family seemed to differentiate Barrett?s esophagus and esophageal adenocarcinoma.

?Therefore, those patients with Barrett?s esophagus with low levels of miR-375 and/or high levels of the other five microRNAs we found to be upregulated in esophageal adenocarcinoma are at increased risk for malignant progression and should be under intensive surveillance, screening and treatment of their Barrett?s esophagus,? Wu noted.

Significant biological insights
?Defining the protein-coding genes targeted by the differentially expressed microRNAs we identified may provide significant biological insights into the development of esophageal adenocarcinoma,? she added. ?Moreover, these genes may themselves become promising biomarkers to predict Barrett?s esophagus progression as well as potential preventive and therapeutic targets.?

For more information
Wu X, Ajani JA, Gu J, Chang DW, Tan W, Hildebrandt MAT, Huang M, Wang KK, Hawk E. MicroRNA Expression Signatures during Malignant Progression from Barrett’s Esophagus to Esophageal Adenocarcinoma.Cancer Prev Res March 2013 6; 196 doi: 10.1158/1940-6207.CAPR-12-0276

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