Membrane bile acid receptor TGR5 predicts good prognosis in ampullary adenocarcinoma patients with hyperbilirubinemia.
Membrane bile acid receptor TGR5 predicts good prognosis in ampullary adenocarcinoma patients with hyperbilirubinemia.
复制标题
DOI：
10.3892/or.2016.5011
复制
发表时间：
2016-10
期刊：
影响因子：
4.2
通讯作者：
Lai MD
中科院分区：
文献类型：
--
作者：
Chen MC;Chen YL;Wang TW;Hsu HP;Lai MD
胆汁酸是胃肠道肿瘤的潜在致癌物，与细胞核和细胞膜受体相互作用，启动下游信号传导。TGR 5 [也称为G蛋白偶联胆汁酸受体1（GPBAR 1）]对癌症进展的影响取决于其被激活的组织。在这份报告中，使用生物信息学方法研究了TGR 5表达在癌症中的功能。通过免疫印迹、逆转录聚合酶链反应和免疫组化（IHC）比较壶腹腺癌和正常十二指肠中TGR 5的表达。GPBAR 1基因高表达是胃癌和乳腺癌患者预后不良的指标，是卵巢癌患者预后较好的指标。GPBAR 1基因表达水平在胆汁酸暴露的癌症中高于其他类型的癌症，并且在高分化壶腹腺癌中增加。TGR 5阴性、弱或轻度表达与年龄、血浆总胆红素/直接胆红素水平、血浆CA-125浓度、肿瘤分期及AJCC TNM分期相关。TGR 5高表达和总胆红素水平高的壶腹腺癌患者的疾病特异性生存率最高。总之，TGR 5在壶腹腺癌和术前高胆红素血症患者中起肿瘤抑制剂的作用。进一步研究其抑制机制可能为壶腹腺癌的治疗提供新的选择。
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.
登录
查看更多内容
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
4.3
作者：
Rostain, Florian;Hamza, Samia;Lepage, Come
通讯作者：
Lepage, Come
影响因子：
4.8
作者：
Jensen, Dane D.;Godfrey, Cody B.;Corvera, Carlos U.
通讯作者：
Corvera, Carlos U.
影响因子：
4.3
作者：
Casaburi, Ivan;Avena, Paola;Ando, Sebastiano
通讯作者：
Ando, Sebastiano
影响因子：
3.4
作者：
Piscuoglio, Salvatore;Lehmann, Frank S.;Terracciano, Luigi M.
通讯作者：
Terracciano, Luigi M.