title: Membrane bile acid receptor TGR5 predicts good prognosis in ampullary adenocarcinoma patients with hyperbilirubinemia.
abstract: Bile acids are potential carcinogens in gastrointestinal cancer, and interact with nuclear and membrane receptors to initiate downstream signaling. The effect of TGR5 [also known as G protein-coupled bile acid receptor 1 (GPBAR1)] on cancer progression is dependent on the tissue where it is activated. In this report, the function of TGR5 expression in cancer was studied using a bioinformatic approach. TGR5 expression in ampullary adenocarcinoma and normal duodenum was compared by western blotting, reverse transcription polymerase chain reaction, and immunohistochemistry (IHC). High GPBAR1 gene expression was found to be an indicator of worse prognosis in gastric and breast cancer patients, and an indication of better prognosis in ovarian cancer patients. The level of GPBAR1 gene expression was higher in bile‑acid exposed cancer than in other types of cancer, and was increased in well-differentiated ampullary adenocarcinoma. Negative, weak or mild expression of TGR5 was correlated with younger age, higher plasma level of total/direct bilirubin, higher plasma concentration of CA-125, advanced tumor stage and advanced AJCC TNM stage. The disease-specific survival rate was highest in ampullary adenocarcinoma patients with high TGR5 expression and high total bilirubin level. In summary, TGR5 functions as a tumor-suppressor in patients with ampullary adenocarcinoma and preoperative hyperbilirubinemia. Further study of the suppressive mechanism may provide a new therapeutic option for patients with ampullary adenocarcinoma.
authors: Department of Surgery, Chi Mei Medical Center, Tainan 710, Taiwan, R.O.C.
authors: Min-Chan
authors: MC
authors: Chen
authors: Department of Senior Citizen Service Management, College of Leisure and Recreation Management, Chia-Nan University of Pharmacy and Science, Tainan 717, Taiwan, R.O.C.
authors: Yi-Ling
authors: YL
authors: Chen
authors: Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan, R.O.C.
authors: Tzu-Wen
authors: TW
authors: Wang
authors: Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan, R.O.C.
authors: Hui-Ping
authors: HP
authors: Hsu
authors: Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan, R.O.C.
authors: Ming-Derg
authors: MD
authors: Lai
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014670:Ampulla of Vater / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D003138:Common Bile Duct Neoplasms / Q000150:complications / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D006932:Hyperbilirubinemia / Q000209:etiology; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D043562:Receptors, G-Protein-Coupled / Q000032:analysis / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C473772:GPBAR1 protein, human; D043562:Receptors, G-Protein-Coupled