Altered expression of TFF-1 and CES-2 in Barrett's Esophagus and associated adenocarcinomas.
Identification of biomarkers to recognize individuals with Barrett's esophagus (BE) predisposed to develop malignancy is currently a pressing issue. We utilized gene expression profiling to compare molecular signatures of normal esophagus and stomach, BE, and adenocarcinoma (AC) to identify such potential biomarkers. Over 22,000 genes were analyzed by oligonucleotide microarrays on 38 unique RNA Unsupervised and supervised clusterings were performed on a subset of 2849 genes that varied most significantly across the specimens. Immunohistochemistry (IHC) for two of the significantly differentially expressed gene products was performed on tissue microarrays. Unsupervised clustering identified two discernable molecular BE profiles, one of which was similar to normal gastric tissue ("BE1"), and another that was shared by several of the AC specimens ("BE2"). The BE1 profile included expression of several genes that have been described as tumor-suppressor genes, most notably trefoil factor 1 (TFF-1). The BE2 profile included expression of genes previously found overexpressed in cancers, such as carboxylesterase-2 (CES-2). IHC demonstrated the loss of TFF-1 late in the progression of BE to AC. It also revealed CES-2 as being upregulated in AC documented to have arisen in the presence of BE. These potential biomarkers, as well as the relative expression of genes from BE1 versus those from BE2, may be validated in the future to aid in risk stratification and guide treatment protocols in patients with BE and associated AC.
Fox
Charles A
CA
Digestive Health Center of Excellence, Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, VA 22908, USA.
Sapinoso
Lisa M
LM
Zhang
Hong
H
Zhang
Wanghai
W
McLeod
Howard L
HL
Petroni
Gina R
GR
Mullick
Tarun
T
Moskaluk
Christopher A
CA
Frierson
Henry F
HF
Hampton
Garret M
GM
Powell
Steven M
SM
D000230:Adenocarcinoma / Q000201:enzymology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001471:Barrett Esophagus / Q000201:enzymology*; D014408:Biomarkers, Tumor; D018826:CD13 Antigens / Q000096:biosynthesis; D002265:Carboxylic Ester Hydrolases / Q000096:biosynthesis*; D004947:Esophagus / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D008957:Models, Genetic; D005810:Multigene Family; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D009841:Oligonucleotides / Q000737:chemistry; D011230:Precancerous Conditions; D012313:RNA / Q000378:metabolism; D018075:RNA, Complementary / Q000378:metabolism; D015398:Signal Transduction; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D014408:Biomarkers, Tumor; D009841:Oligonucleotides; D018075:RNA, Complementary; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D012313:RNA; D002265:Carboxylic Ester Hydrolases; C474609:CES1 protein, human; D018826:CD13 Antigens