胰腺癌相关糖尿病致病基因表达谱的分析  

Analysis of gene expression profiles related to pathogenesis of pancreatic cancer associated diabetes

作　　者：林青[1] 李志花[2] 郑上游[1] 周泉波[1] 谭浪平[1] 李国林[1] 宋亚东[2] 赵晓慧[2] 高文超[1] 陈汝福[1] 

机构地区：[1]中山大学孙逸仙纪念医院胆胰外科,广州510120 [2]中山大学孙逸仙纪念医院肿瘤科,广州510120

出　　处：《中华胰腺病杂志》2015年第5期319-324,共6页Chinese Journal of Pancreatology

基　　金：广东省自然科学基金（S2012010008934）

摘　　要：目的探讨胰腺癌相关糖尿病（PCA—DM）致病基因的表达谱，为PCA—DM发病机制的研究提供新线索。方法对前期获得的4例PCA—DM患者、4例无糖尿病胰腺癌（PC）患者和4例慢性胰腺炎（CP）患者胰腺组织基因芯片分析结果进一步进行盒图、火山图、热图分析；基因相互作用网络分析；染色体定位分析；Geneontology（GO）分析，并采用实时PCR对差异表达基因进行验证。结果芯片检测质量可靠。PCA-DM与无糖尿病Pc差异表达基因共2778个，其中表达倍数差异〉10的有123个基因；无糖尿病Pc与cP差异表达基因共7475个，其中表达倍数差异〉10的有730个。PCA—DM与无糖尿病PC差异表达基因的数量及差异倍数明显少于无糖尿病PC与CP的差异表达基因。PCA—DM和无糖尿病Pc的差异表达基因大多分布于PC与CP差异表达基因的染色体位点上。GO分析显示，与药物代谢、色素沉着、GTPase活性有关的条目上调，而与蛋白代谢、核酸代谢有关的条目下调。在PCA—DM相关基因网络中，HSPA1A、CSNK1A1、EIF4A2、MYCBP2、PRKRA、NGFR等40个基因参与PCA-DM发生。TFF1、MSMB、NOX1等13个基因对PCA—DM具有潜在诊断价值。结论建立了PCA—DM致病基因表达谱，发现了潜在的致病基因及具有潜在诊断价值的基因。Objective To explore the gene expression profiles related to pathogenesis of pancreatic cancer associated diabetes （PCA-DM） and provide new clues for the study of PCA-DM. Methods The tissues of four patients with pancreatic ductal adenocarcinoma with diabetes （ PCA-DM ）, four patients with pancreatic ductal adenocarcinoma without diabetes （PC） and four patients with chronic pancreatitis （CP） were analyzed by microarrays individually, and following box diagram, volcano diagram, heat map analysis, gene interaction network analysis; chromosome positioning analysis, gene ontology （GO） analysis, and RT-PCR was used to confirm the results. ResUlts Data showed that the microarray analysis was well controlled in quality. There were 2 778 differentially expressed genes of pancreatic cancer tissues between PCA-DM and PC individuals, among them, there were 123 genes with difference expression 〉 l0 folds; and there were 7 475 differentially expressed genes between PC and CP, among them, there were 730 genes with difference expression 〉 10 folds. The differentially expressed genes between PCA-DM and PC individuals were less than those of PC and CP in quantity and fold changes. Furthermore, the majority of differentially expressed genes between PCA-DM and PC were located near the PC and CP on the genome. GO analysis demonstrated that the overrepresented items included drug catabolic process, pigmentation, GTPase activity. The decreased GO items included protein metabolic process, protein binding. Gene network analysis indicated that a total of 40 genes including HSPA1A, CSNK1AI ,EIF4A2 , MYCBP2, PRKRA and NGFR may be related the pathogenesis of PCA-DM. Totally 13 genes including TFF1, MSMB, NOX1 were of potential diagnostic value to PCA-DM. Conclusions Pathogenic gene expression profiles of PCA-DM is established, potential causative genes and genes of potential diagnostic value are discovered.

关 键 词：胰腺肿瘤 糖尿病 基因表达谱 芯片分析技术 

分 类 号：R735.9[医药卫生—肿瘤] R587.1[医药卫生—临床医学]