Bile salt receptor TGR5 is highly expressed in esophageal adenocarcinoma and precancerous lesions with significantly worse overall survival and gender differences
Chunhong Pang,1,2 Amy LaLonde,3 Tony E Godfrey,4 Jianwen Que,5,6 Jun Sun,7 Tong Tong Wu,3 Zhongren Zhou2 1Department of Pathology, China-Japan Friendship Hospital, 2Department of Pathology and Laboratory Medicine, 3Department of Biostatistics and Computational Biology, University of Rochester, Roche...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2017-02-01
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| Series: | Clinical and Experimental Gastroenterology |
| Subjects: | |
| Online Access: | https://www.dovepress.com/bile-salt-receptor-tgr5-is-highly-expressed-in-esophageal-adenocarcino-peer-reviewed-article-CEG |
| _version_ | 1818205641492135936 |
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| author | Pang CH LaLonde A Godfrey TE Que J Sun J Wu TT Zhou ZR |
| author_facet | Pang CH LaLonde A Godfrey TE Que J Sun J Wu TT Zhou ZR |
| author_sort | Pang CH |
| collection | DOAJ |
| description | Chunhong Pang,1,2 Amy LaLonde,3 Tony E Godfrey,4 Jianwen Que,5,6 Jun Sun,7 Tong Tong Wu,3 Zhongren Zhou2 1Department of Pathology, China-Japan Friendship Hospital, 2Department of Pathology and Laboratory Medicine, 3Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY, 4Department of Surgery, Boston University Medical Center, Boston, MA, 5Center for Human Development, 6Division of Digestive and Liver Diseases, Columbia University, New York, NY, 7Division of Gastroenterology and Hepatology, University of Illinois College of Medicine, Chicago, IL, USA 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. The TGR5 gene 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. Keywords: esophageal adenocarcinoma, Barrett’s esophagus, TGR5, bile acid receptor, amplification |
| first_indexed | 2024-12-12T04:00:22Z |
| format | Article |
| id | doaj.art-ab13c92353cb40e3920006c27fbc247d |
| institution | Directory Open Access Journal |
| issn | 1178-7023 |
| language | English |
| last_indexed | 2024-12-12T04:00:22Z |
| publishDate | 2017-02-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Clinical and Experimental Gastroenterology |
| spelling | doaj.art-ab13c92353cb40e3920006c27fbc247d2022-12-22T00:39:05ZengDove Medical PressClinical and Experimental Gastroenterology1178-70232017-02-01Volume 10293731167Bile salt receptor TGR5 is highly expressed in esophageal adenocarcinoma and precancerous lesions with significantly worse overall survival and gender differencesPang CHLaLonde AGodfrey TEQue JSun JWu TTZhou ZRChunhong Pang,1,2 Amy LaLonde,3 Tony E Godfrey,4 Jianwen Que,5,6 Jun Sun,7 Tong Tong Wu,3 Zhongren Zhou2 1Department of Pathology, China-Japan Friendship Hospital, 2Department of Pathology and Laboratory Medicine, 3Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY, 4Department of Surgery, Boston University Medical Center, Boston, MA, 5Center for Human Development, 6Division of Digestive and Liver Diseases, Columbia University, New York, NY, 7Division of Gastroenterology and Hepatology, University of Illinois College of Medicine, Chicago, IL, USA 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. The TGR5 gene 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. Keywords: esophageal adenocarcinoma, Barrett’s esophagus, TGR5, bile acid receptor, amplificationhttps://www.dovepress.com/bile-salt-receptor-tgr5-is-highly-expressed-in-esophageal-adenocarcino-peer-reviewed-article-CEGesophageal carcinomaBarrett's esophagusThe G-protein coupled bile acid receptoramplification |
| spellingShingle | Pang CH LaLonde A Godfrey TE Que J Sun J Wu TT Zhou ZR Bile salt receptor TGR5 is highly expressed in esophageal adenocarcinoma and precancerous lesions with significantly worse overall survival and gender differences Clinical and Experimental Gastroenterology esophageal carcinoma Barrett's esophagus The G-protein coupled bile acid receptor amplification |
| title | Bile salt receptor TGR5 is highly expressed in esophageal adenocarcinoma and precancerous lesions with significantly worse overall survival and gender differences |
| title_full | Bile salt receptor TGR5 is highly expressed in esophageal adenocarcinoma and precancerous lesions with significantly worse overall survival and gender differences |
| title_fullStr | Bile salt receptor TGR5 is highly expressed in esophageal adenocarcinoma and precancerous lesions with significantly worse overall survival and gender differences |
| title_full_unstemmed | Bile salt receptor TGR5 is highly expressed in esophageal adenocarcinoma and precancerous lesions with significantly worse overall survival and gender differences |
| title_short | Bile salt receptor TGR5 is highly expressed in esophageal adenocarcinoma and precancerous lesions with significantly worse overall survival and gender differences |
| title_sort | bile salt receptor tgr5 is highly expressed in esophageal adenocarcinoma and precancerous lesions with significantly worse overall survival and gender differences |
| topic | esophageal carcinoma Barrett's esophagus The G-protein coupled bile acid receptor amplification |
| url | https://www.dovepress.com/bile-salt-receptor-tgr5-is-highly-expressed-in-esophageal-adenocarcino-peer-reviewed-article-CEG |
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