Expression And Clinical Significance Of Hypoxia Inducible Factors In Pancreatic Cancer

Objective: to study the expression and clinical significance of hypoxia inducible factors(HIF-1,HIF-2,HIF-3)in pancreatic cancer.Methods: 1.The Oncomine database was used to investigate the differential expression of hypoxia inducible factors(including HIF1 A,ARNT,EPAS1,and HIF3A)in pancreatic cancer tissues and normal pancreatic tissues,and to explore the 10 genes with the largest correlation coefficient of each gene.2.The DAVID database was used to study the GO process and the KEGG signaling pathway that hypoxia inducible factors(including HIF1 A,ARNT,EPAS1,HIF3A)involve in.3.The GEPIA online analysis tool was used to study the relationship between the expression of hypoxia inducible factors(including HIF1 A,ARNT,EPAS1 and HIF3A)and the clinical stage,overall survival and disease-free survival of pancreatic cancer patients.4.Western blot assay was used to validate the differences of HIF-1? protein expression levels in pancreatic cancer tissues and normal pancreatic tissues.5.Polymerase chain reaction assay was used to verify the differences of HIF-1? and HIF-2? m RNA expression levels in pancreatic cancer tissues and normal pancreatic tissues.6.Immunohistochemical staining assay was used to verify the expression differences of HIF-1? protein in pancreatic cancer tissues and normal pancreatic tissues.Conclusion: 1.The study of hypoxia inducible factors(including HIF1 A,ARNT,EPAS1,and HIF3A)in the Oncomine database found that the expression levels of HIF1 A,ARNT,EPAS1,and HIF3 A in pancreatic cancer tissues were all higher than those in normal pancreatic tissues,and the statistical index were 0.006,6.06E-6,0.046,and 0.024,respectively,all that < 0.05.2.Genes synergistically expressed with hypoxia inducible factors(including HIF1 A,ARNT,EPAS1,HIF3A)were studied by Oncomine database.Among them,the 10 genes with the largest correlation coefficient with HIF1 A were PFKFB3,ACSL4,C3orf64,AEBP2,SNORD89,GNS,RP2,UBE2D1,RNF149,and PGM2.The 10 genes with the largest correlation coefficient with ARNT were SETDB1,CTSK,LASS2,ANXA9,FAM63 A,PRUNE,C1orf56,BNIPL,TNFAIP8L2 and LYSMD1.The 10 genes with the largest correlation coefficients with EPAS1 were PPAP2 A,NFIB,PPAP2 B,KLF9,PER2,MAN1A1,ADD3,CE302,NEAT1,SFRS3.The 10 genes with the largest correlation coefficients with HIF3 A were CALM3,PTGIR,GNG8,DACT3,PRKD2,STRN4,FKRP,SLC1A5,AP2S1,and PPP5 C.3.Through the DAVID database,it was found that hypoxia inducible factors had transcriptional factor activity and were DNA specific binding sequences;It is a component of RNA polymerase II transcription factor complex and nuclear speck;It plays a role in transcription,DNA templating,hormone biosynthesis,embryonic placenta development,positive regulation of vascular endothelial growth factor and hypoxia response.It is also involved in renal cell carcinoma,cancer pathway and HIF-1? signaling pathway.4.It was found by the GEPIA analysis tool that the expression levels of hypoxia inducible factors(including HIF1 A,ARNT,EPAS1 and HIF3A)were independent with the clinical staging of pancreatic cancer patients.The expression levels of hypoxia inducible factors(including HIF1 A,ARNT,EPAS1 and HIF3A)were not correlated with the overall survival of pancreatic cancer patients.The expression levels of hypoxia inducible factors(including HIF1 A,ARNT,EPAS1 and HIF3A)were not correlated with disease-free survival of pancreatic cancer patients.All statistical index were > 0.05.5.Western blotting assay confirmed that HIF-1? protein expression level in pancreatic cancer tissues was higher than that in normal pancreatic tissues,P value < 0.05.6.Polymerase chain reaction assay confirmed the expression levels of HIF-1? and HIF-2? m RNA in pancreatic cancer tissues were higher than that in normal pancreatic tissues,P value < 0.05.7.Immunohistochemical staining assay confirmed that HIF-1? protein expression level in pancreatic cancer tissues was higher than that in normal pancreatic tissues,P value < 0.05.