Correlation analysis between period circadian clock 2 gene and the prognosis of pancreatic ductal adenocarcinoma

Abstract

Objective To explore the prognosis related genes of pancreatic ductal adenocarcinoma （PDAC）and investigate the molecular regulation mechanism.Methods Gene expression data of 102 PDAC patients with complete clinical survival data were selected from gene expression database of National Center for Biotechnology Information.The 106 transcription regulation gene collection was collected from Transfac database.The 715 microRNA （miRNA）target regulation gene collection was selected according to PicTar and TargetScanS method.Biological pathway data obtained from the Kyoto Encyclopedia of Genes and Genomes （KEGG）.The known cancer genes were collected from the cancer gene census （CGC） database.Univariate Cox proportional hazards model was used to analyze the correlation between gene expression data and survival time,then obtained survival related candidate genes from the whole genome. Then the enriched genes were analyzed by hypergeometric distribution algorithm from three databases. Multiple correction testing was performed by BH-FDR method （FDR 〈 0.05 ）.Kaplan-Meier was performed for survival curve analysis of PDAC.Results The results of data of 102 PDAC patients analyzed by univariate Cox proportional hazards model indicated that 273 genes were significantly related to the survival time of patients （P 〈0.000 1 ）.After 273 survival genes were enrichment analyzed in 106 transcription factor regulation gene collection,12 survival genes enriched transcription factor target gene sets were found.After 273 survival genes were enrichment analyzed in 715 miRNA target regulation gene collection,11 survival genes enriched miRNAs target sets were discovered.After 273 survival genes were enrichment analyzed in pathway data of KEGG,15 survival genes enriched pathways were obtained. Period circadian clock 2 （PER2 ）was regulated by CCAAT/enhancer binding protein （CEBPA）at transcription level and regulated by miRNA-32 after transcription.The prognosis of PDAC was affected by circadian rhythm pathway.The 102 patients with PDAC were ranked according to the expression of PER2 from high to low,the first 51 cases were included in PER2 higher expression group and the left were included in PER2 lower expression group.Kaplan-Meier survival analysis indicated that PER2 was significantly correlated with prognosis of PDAC （P 〈0.01 ）.Conclusion CEBPA/miRNA-32/PER2 and its related circadian clock pathway may be the target pathway in interfering the development of PDAC,and is correlated with the prognosis of PDAC. Key words: Pancreatic ductal adenocarcinoma; PER2; Prognosis; Molecule mechanism