Meta-Analysis Reveals the Prognostic Relevance of Nuclear and Membrane-Associated Bile Acid Receptors in Gastric Cancer.
Meta-Analysis Reveals the Prognostic Relevance of Nuclear and Membrane-Associated Bile Acid Receptors in Gastric Cancer.
复制标题
DOI：
10.14309/ctg.0000000000000295
复制
发表时间：
2021-01-12
影响因子：
3.6
通讯作者：
Altomare DA
中科院分区：
文献类型：
--
作者：
Rohr M;Aljabban J;Rudeski-Rohr T;Lessans S;Nakkina SP;Hadley D;Zhu X;Altomare DA
已知由胃反流引起的胆汁酸（BA）促进胃癌（GC）的发展。虽然BA传统上通过直接细胞毒性促进致癌作用，但越来越多的证据表明核和膜BA受体（BAR）是影响癌症风险的额外因素。事实上，一些BAR已经与GC相关联，但相互矛盾的证据和缺乏关于其他内源性BAR的信息需要进一步调查。在这项研究中，我们荟萃分析了多个数据集，以确定临床相关的关系，BAR表达和预后，临床病理学，和活动在GC。我们从基因表达综合库和癌症基因组图谱中收集转录组数据，分析BAR表达与胃癌预后、亚型和临床病理学之间的关系。我们还使用了免疫途径分析来评估和预测GC中膜和核BAR的功能、上游调节因子和下游介质。BAR在GC中表现出差异性分布;膜BAR（G蛋白偶联BAR 1、鞘氨醇-1-磷酸受体2和胆碱能受体毒蕈碱2）在弥漫型、基因组稳定型和间质型肿瘤中富集，而核BAR（孕烷-X-受体、组成型雄烷受体和法尼醇-X-受体）在染色体不稳定性和代谢亚型中富集。所有膜而非核BAR的高表达与不良预后和不利的GC临床病理特征相关。类似地，膜而非核BAR的表达模式在地理上不同，与幽门螺杆菌感染和GC死亡率一致。最后，GC相关癌基因，即转化生长因子β1，与膜BAR相关，而许多代谢相关基因与核BAR相关。通过转录组学荟萃分析，我们确定了核和膜BAR之间的不同表达谱，证明了预后相关性，并需要进一步研究。
Bile acids (BAs) arising from duodenogastric reflux are known to facilitate gastric cancer (GC) development. Although BAs traditionally contribute to carcinogenesis through direct cellular cytotoxicity, increasing evidence implicates nuclear and membrane BA receptors (BARs) as additional factors influencing cancer risk. Indeed, some BARs are already linked with GC, but conflicting evidence and lack of information regarding other endogenous BARs warrant further investigation. In this study, we meta-analyzed multiple data sets to identify clinically relevant relationships between BAR expression and prognosis, clinicopathology, and activity in GC. We collected transcriptomic data from the Gene Expression Omnibus and The Cancer Genome Atlas to analyze associations between BAR expression and GC prognosis, subtype, and clinicopathology. We also used Ingenuity Pathway Analysis to assess and predict functions, upstream regulators, and downstream mediators of membrane and nuclear BARs in GC. BARs showed differential distribution in GC; membrane BARs (G protein-coupled BAR 1, sphingosine-1-phosphate receptor 2, and cholinergic receptor muscarinic 2) were enriched in diffuse-, genome-stable, and mesenchymal-type tumors, whereas nuclear BARs (pregnane-X-receptor, constitutive androstane receptor, and farnesoid-X-receptor) were enriched in chromosome instability and metabolic subtypes. High expression of all membrane but not nuclear BARs was associated with poor prognosis and unfavorable GC clinicopathologic features. Similarly, expression patterns of membrane but not nuclear BARs varied geographically, aligning with Helicobacter pylori infection and GC mortality rates. Finally, GC-related oncogenes, namely transforming growth factor β1, were associated with membrane BARs, whereas many metabolic-associated genes were associated with nuclear BARs. Through transcriptomic meta-analysis, we identified distinct expression profiles between nuclear and membrane BARs that demonstrate prognostic relevance and warrant further investigation.
登录
查看更多内容
DOI：
10.1097/pai.0000000000000199
发表时间：
2016-05-01
影响因子：
1.6
作者：
Han, Nayoung;Kim, Min A.;Kim, Woo Ho
通讯作者：
Kim, Woo Ho
影响因子：
4.2
作者：
Chen MC;Chen YL;Wang TW;Hsu HP;Lai MD
通讯作者：
Lai MD
DOI：
10.1016/0197-2456(86)90046-2
发表时间：
1986-09-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
--
作者：
DERSIMONIAN, R;LAIRD, N
通讯作者：
LAIRD, N
影响因子：
6
作者：
Bi, Yan;Li, Jiachu;Shah, Vijay
通讯作者：
Shah, Vijay
影响因子：
2.7
作者：
Cheng L;Wang P;Yang S;Yang Y;Zhang Q;Zhang W;Xiao H;Gao H;Zhang Q
通讯作者：
Zhang Q