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基于TCGA数据库分析SLC5A1在胰腺癌中的表达及潜在促癌作用
SLC5A1 as a potential target in pancreatic cancer:the preliminary clue from TCGA data
【摘要】 目的 基于癌症基因组图谱(the cancer genome atlas, TCGA)数据库分析溶质载体家族5-成员1(solute carrier family 5-member 1,SLC5A1)在胰腺癌中的表达及其与临床病理、预后的相关性,探索其在胰腺癌发生、进展中的作用。方法利用GEPIA分析TCGA数据库中胰腺癌数据,比较SLC5A1在胰腺癌及正常胰腺组织中的表达情况,同时利用LinkedOmics和GEPIA分析其在胰腺癌中表达与不同临床病理特征的相关性;利用cBioPortal和LinkedOmics分析胰腺癌中与SLC5A1表达相关的基因,并利用DAVID和KEGG进行信号通路聚类;探讨SLC5A1与胰腺癌不同基因亚型标志物表达的相关性。结果SLC5A1 mRNA表达在胰腺癌组织显著高于非胰腺癌组织(P<0.05)。在胰腺癌中与SLC5A1高表达相关的基因大多位于细胞膜和细胞核,负责蛋白和离子的结合,参与细胞生物功能、代谢调节,其高表达与葡萄糖摄取、糖酵解/糖异生、胰腺分泌等的基因信号通路呈正相关。SLC5A1的表达与胰腺癌异常分化的内分泌外分泌(aberrantly differentiated endocrine exocrine,ADEX)亚型的胰岛素(insulin,INS)、核受体亚家族5-组A-成员2(nuclear receptor subfamily 5-group A-member 2,NR5A2)和蛋白酶-丝氨酸-3(protease-serine-3,PRSS3)表达呈正相关,差异有统计学意义;与胰腺祖细胞型叉头框A3(forkhead box A3,FOXA3)、肝细胞核因子1α(hepatocyte nuclear factor 1-alpha,HNF1A)、叉头框A2(forkhead box A2,FOXA2)、肝细胞核因子1β(hepatocyte nuclear factor 1β,HNF1B)、胰十二指肠同源框因子-1(pancreatic and duodenal homeobox 1,PDX1)、肝细胞核因4-γ(hepatocyte nuclear factor 4-gamma,HNF4G)、肝细胞核因子4-α(hepatocyte nuclear factor 4-alpha,HNF4A)、多毛和增强子断裂1(hairy and enhancer of split 1,HES1)表达均呈正相关,且差异有统计学意义(P<0.05)。结论 SLC5A1在胰腺癌中高表达;其高表达与葡萄糖摄取、糖酵解、胰腺分泌的基因信号通路呈正相关,与胰腺癌祖细胞亚型及ADEX亚型密切相关。
【Abstract】 Objective To analyze the expression of SLC5A1 in pancreatic cancer and its correlation with clinicopathologic features and prognosis,and also to explore its role in the tumor genesis and development of pancreatic cancer(PC).Methods The m RNA expression of SLC5A1 in normal pancreatic tissues and PC from TCGA data was compared using GEPIA.The expressions of SLC5A1 were compared between PC and normal pancreatic tissue.At the same time,its expression in PC and correlation of different clinicopathologic features were investigated by using Linked Omics and GEPIA.The genes related to the expression of SLC5A1 in PC were analyzed using c Bio Portal and Linked Omics,and the genes were clustered using DAVID and KEGG.The correlation between SLC5A1 and the different sub-types of PC was also explored.Results The m RNA expression of SLC5A1 in pancreatic cancer tissues was significantly higher than that in non-pancreatic cancer tissues(P<0.05).In PC,the molecules related to SLC5A1 were mostly located in the cell membrane and nucleus,and were responsible for the protein and ion nuclear acid binding,involved in cell biological function and metabolic regulation.The high expression of SLC5A1 was positively related with glucose uptake,glycolysis/gluconeogenesis and pancreatic secretion signal pathways.The expression of SLC5A1 was positively correlated with the expression of NR5A2 and PRSS3 of the aberrantly differentiated endocrine exocrine(ADEX)sub-type of PC,with statistical significance(P<0.05).Its expression was positively correlated with the expression of forkhead box A3(FOXA3),hepatocyte nuclear factor 1-alpha(HNF1A),forkhead box A2(FOXA2),hepatocyte nuclear factor1β(HNF1B),pancreatic and duodenal homeobox 1(PDX1),hepatocyte nuclear factor 4-gamma(HNF4G),hepatocyte nuclear factor 4-alpha(HNF4A)and hairy and enhancer of split 1(HES1),also with statistical significance(P<0.05).Conclusion There is over-expression of SLC5A1 in PC.Its high expression is positively correlated with glucose uptake,glycolysis and pancreatic secretion signal pathway,and the high expression of SLC5A1 is closely related to progenitor and ADEX sub-types of PC.
【Key words】 Pancreatic cancer; Pancreatic ductal adenocarcinoma; SGLT-1; SLC5A1; The cancer genome atlas;
- 【文献出处】 海军医学杂志 ,Journal of Navy Medicine , 编辑部邮箱 ,2022年07期
- 【分类号】R735.9
- 【被引频次】1
- 【下载频次】100