title: Bile salt receptor TGR5 is highly expressed in esophageal adenocarcinoma and precancerous lesions with significantly worse overall survival and gender differences.
abstract: Bile acid reflux in the esophagus plays an important role in the carcinogenesis of esophageal adenocarcinoma (EAC). The G-protein coupled bile acid receptor (TGR5) has been associated with the development of gastrointestinal cancer. However, little is known regarding the role of TGR5 in esophageal carcinoma and precancerous lesions. We analyzed genomic DNA from 116 EACs for copy number aberrations via Affymetrix SNP6.0 microarrays. TheTGR5gene locus was amplified in 12.7% (14/116) of the EACs. The TGR5 protein expression was also assessed using immunohistochemistry from tissue microarrays, including Barrett's esophagus (BE), low-(LGD) and high-grade dysplasia (HGD), columnar cell metaplasia (CM), squamous epithelium (SE), EAC and squamous cell carcinoma. The TGR5 protein was highly expressed in 71% of EAC (75/106), 100% of HGD (11/11), 72% of LGD (13/18), 66% of BE (23/35), 84% of CM (52/62), and 36% of SE (30/83). The patients with high expression of TGR5 exhibited significantly worse overall survival compared to the patients with nonhigh expression. TGR5 high expression was significantly increased in the males compared to the females in all cases with an odds ratio of 1.9 times. The vitamin D receptor (VDR) was significantly correlated with TGR5 expression. Our findings indicated that TGR5 may play an important role in the development and prognosis of EAC through a bile acid ligand. Gender differences in TGR5 and VDR expression may explain why males have a higher incidence of EAC compared to females.
authors.affiliation: Department of Pathology, China-Japan Friendship Hospital; Department of Pathology and Laboratory Medicine.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Pang
authors.affiliation: Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY.
authors.forename: Amy
authors.initials: A
authors.lastname: LaLonde
authors.affiliation: Department of Surgery, Boston University Medical Center, Boston, MA.
authors.forename: Tony E
authors.initials: TE
authors.lastname: Godfrey
authors.affiliation: Center for Human Development; Division of Digestive and Liver Diseases, Columbia University, New York, NY.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Que
authors.affiliation: Division of Gastroenterology and Hepatology, University of Illinois College of Medicine, Chicago, IL, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY.
authors.forename: Tong Tong
authors.initials: TT
authors.lastname: Wu
authors.affiliation: Department of Pathology and Laboratory Medicine.
authors.forename: Zhongren
authors.initials: Z
authors.lastname: Zhou
keywords: Barrett’s esophagus; TGR5; amplification; bile acid receptor; esophageal adenocarcinoma