title: Deciphering the unique microRNA signature in human esophageal adenocarcinoma.
abstract: METHODS
  Esophageal adenocarcinoma (EAC) is characterized by a steep rise in incidence rates in the Western population. The unique miRNA signature that distinguishes EAC from other upper gastrointestinal cancers remains unclear. Herein, we performed a comprehensive microarray profiling for the specific miRNA signature associated with EAC. We validated this signature by qRT-PCR.
  
  
  RESULTS
  Microarray analysis showed that 21 miRNAs were consistently deregulated in EAC. miR-194, miR-192, miR-200a, miR-21, miR-203, miR-205, miR-133b, and miR-31 were selected for validation using 46 normal squamous (NS), 23 Barrett's esophagus (BE), 17 Barrett's high grade dysplasia (HGD), 34 EAC, 33 gastric adenocarcinoma (GC), and 45 normal gastric (NG) tissues. The qRT-PCR analysis indicated that 2 miRNAs (miR-21 and miR-133b) were deregulated in both EAC and GC, and 6 miRNAs (up-regulated: miR-194, miR-31, miR-192, and miR-200a; down-regulated: miR-203 and miR-205) in EAC, as compared to BE but not in GC, indicating their potential unique role in EAC. Our data showed that miR-194, miR-192, miR-21, and miR-31 were up-regulated in BE adjacent to HGD lesions relative to isolated BE samples. Analysis of clinicopathological features indicated that down-regulation of miR-203 is significantly associated with progression and tumor stages in EAC. Interestingly, the overexpression levels of miR-194, miR-200a, and miR-192 were significantly higher in early EAC stages, suggesting that these miRNAs may be involved in EAC tumor development rather than progression.
  
  
  CONCLUSIONS
  Our findings demonstrate the presence of a unique miRNA signature for EAC. This may provide some clues for the distinct molecular features of EAC to be considered in future studies of the role of miRNAs in EAC and their utility as disease biomarkers.
authors.affiliation: Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Rama
authors.initials: R
authors.lastname: Saad
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chen
authors.forename: Shoumin
authors.initials: S
authors.lastname: Zhu
authors.forename: Peilin
authors.initials: P
authors.lastname: Jia
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhao
authors.forename: M Kay
authors.initials: MK
authors.lastname: Washington
authors.forename: Abbes
authors.initials: A
authors.lastname: Belkhiri
authors.forename: Wael
authors.initials: W
authors.lastname: El-Rifai
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D001471:Barrett Esophagus / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D035683:MicroRNAs