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

作　　者：陈谱[1] 袁黎玥 雷雨阳 张曈欣 袁佳 郭辉[1] 施秉银[1] 强薇[1] Chen Pu;Yuan Liyue;Lei Yuyang;Zhang Tongxin;Yuan Jia;Guo Hui;Shi Bingyin;Qiang Wei(Department of Endocrinology,First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China)

机构地区：[1]西安交通大学第一附属医院内分泌科,陕西西安710061 [2]西安交通大学第一附属医院心血管内科 [3]民航西安医院急诊科

出　　处：《海军医学杂志》2022年第7期708-714,共7页Journal of Navy Medicine

基　　金：国家自然青年基金(81802829);陕西省自然基础研究项目(2020JQ-501)。

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�Objective To analyze the expression of SLC5A1 in pancreatic cancer and its correlation with clinicopathologic fea-tures and prognosis,and also to explore its role in the tumor genesis and development of pancreatic cancer(PC).Methods The mRNA 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 LinkedOmics and GEPIA.The genes related to the expression of SLC5A1 in PC were analyzed using cBioPortal and LinkedOmics,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 mRNA 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 mem-brane 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 secre-tion 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 corre-lated with the expression of forkhead box A3(FOXA3),hepatocyte nuclear factor 1-alpha(HNF1A),forkhead box A2(FOXA2),he-patocyte 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 si

关 键 词：胰腺癌 胰腺导管癌 钠糖共转运蛋白-1 溶质载体家族5-成员1 癌症基因组图谱 

分 类 号：R735.9[医药卫生—肿瘤]