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Gene Expression Profiling In Chronic Pancreatitis-Pancreatic Carcinoma-Metastatic Pancreatic Carcinoma

Posted on:2021-03-08Degree:MasterType:Thesis
Country:ChinaCandidate:Z K YinFull Text:PDF
GTID:2404330632950486Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
For pancreatic cancer,which the deadliest malignant diseases,there has been poor progress in the development of new effective treatments.Surgical resection is still the only effective treatment to date.However,only about 20% of patients have a chance of surgical resection at the time of diagnosis.Therefore,it is important to look for specific biomarkers to predict a patient's prognosis.Exploring the underlying mechanisms of cancer development is useful to cancer treatment.Since Inflammation and cancer are both systems biology disease,relationship between inflammation and cancer can be characterize by systems biology approach.In this paper,we analyzed the transcriptome profiles from human pancreatitis-pancreatic cancer-metastatic pancreatic cancer to study the intricate associations among pancreatic cancer progression.We cluster the transcriptome data,analyzed the differential expressed genes and enriched them.The number of differential expressed genes increases and the biological process,cell component,molecular function,site of expression and biological process change as the pancreatic disease deteriorates.Immune response and cell growth and/or maintenance are in all the pancreatic cancer progression.We found differential expressed genes by significance analysis of microarrays could be markers to differentiate human pancreatitis-pancreatic cancer-metastatic pancreatic cancer.In conclusion,the network-based study provides multiple evidences for the intricate relationship between pancreatitis,pancreatic cancer and metastatic pancreatic cancer.However,the exact role of the predicted genes remains to be elucidated in pancreatic cancer.Objectives:To explore the relationship between chronic pancreatitis-pancreatic cancermetastasis pancreatic cancer on the transcriptome,clarify the relationship between pancreatitis-related genes and the pathological characteristics of pancreatic cancer and metastatic pancreatic cancer,and provide evidence for the diagnosis and prognosis of patients with pancreatic cancer.Methods: Use the gene expression profile of human pancreatic samples from the European Institute of Bioinformatics database(including 9 normal pancreatic samples,9 chronic pancreatitis patient samples,9 pancreatic cancer patient samples,and 9 metastatic pancreatic cancer patient samples)for aggregation Class analysis,differentially expressed gene screening(using fold change | log2 Fold Change |> 1,false discovery rate FDR<0.05 is the threshold),functional enrichment analysis,biomolecular network construction,network topology analysis,to determine candidate genes;using The Human Protein Atlas database and GEPIA database confirm the prognostic evaluation value of candidate gene expression level for pancreatic cancer patients.Results: 1.Compared with normal pancreas,there are 965 differential expressed genes(DEG)in chronic pancreatitis,2,060 in pancreatic cancer,and 2,517 in metastatic pancreatic cancer;chronic pancreatitis and pancreatic cancer There are 741 overlapping DEGs,accounting for 35.97% of pancreatic cancer DEG;pancreatic cancer and metastatic pancreatic cancer have 1315 DEG overlapping,accounting for 52.24% of metastatic pancreatic cancer DEG;chronic pancreatitis and metastatic pancreatic cancer have 656 DEG overlapping,accounting for metastasis 31.84% of DEG in pancreatic cancer;among chronic pancreatitis,pancreatic cancer and metastatic pancreatic cancer,573 DEG overlap.It is suggested that through the SAM method,302 statistically significant DEGs were differentially expressed in the four stages of normal state,chronic pancreatitis,pancreatic cancer and metastatic pancreatic cancer.2.IL6,FN1,ALB,PTPRC,CXCL8,VCAM1,TIMP1,ACTB,ITGB2,COL1A1,FYN,RAC2,CXCL8 and PTGS2 play a key role in the process of pancreatitispancreatic cancer-metastatic pancreatic cancer.3.Through the analysis of The Human Protein Atlas database and GEPIA database,it was found that the overall survival of pancreatic cancer patients with high FYN expression was significantly longer than that of pancreatic cancer patients with low FYN expression(P<0.05).Conclusions: 1.There is a correlation between chronic pancreatitis,pancreatic cancer and metastatic pancreatic cancer.2.The expression levels of protein metabolism,energy pathways and ribosome biosynthesis are significantly changed in pancreatitis-pancreatic cancer-pancreatic cancer tissues.3.The higher the expression level of FYN protein,the better the prognosis of pancreatic cancer patients.FYN is expected to become a biomarker for early diagnosis and prognosis of pancreatic cancer.
Keywords/Search Tags:Pancreatic carcinoma, Pancreatitis-pancreatic cancer-pancreatic cancer, Transcriptomics, Diagnosis, Prognosis
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