Identification of Disease-specific Genes in Chronic Pancreatitis Using DNA Array Technology

Abstract

ObjectiveTo use DNA arrays to analyze the differential gene expression patterns in the normal pancreas and in pancreatic diseases. Summary Background DataGenome-wide gene expression analysis will provide new insights into gene function and cause of disease. MethodsRNA was extracted from eight normal pancreatic specimens, eight specimens with chronic pancreatitis (CP), and eight pancreatic cancer (PCa) tissues. Poly A(ϩ) RNA was purified, reverse-transcribed, and converted into cRNA using biotinylated nucleotides. The HuGeneFL DNA array containing 5,600 fulllength human genes was used for analysis. ResultsFirst, normal pancreatic tissues were analyzed in comparison with a panel of other normal tissues (colon, liver, prostate, lung, lymph node). This analysis revealed 11 signature genes that were selectively expressed in the pancreas (e.g., pancreatic elastase-IIA). Comparison of the expression of 5,600 genes between the normal pancreas, CP, and PCa specimens showed that the expression of 34 genes was decreased in CP tissues compared with normal pancreatic tissues, and that the expression of all of these genes was simultaneously decreased in PCa. In addition, the expression of 157 genes was increased in CP tissues compared with the normal pancreas. Of those, 152 genes were simultaneously increased in PCa. Thus, only 5 of 5,600 genes were significantly overexpressed in CP compared with both normal pancreas and PCa. ConclusionsThe majority of alterations observed in CP are present in PCa, and the number of genes whose expression is selectively deregulated in CP is surprisingly small. These results may provide new insight into the pathobiology of CP and help identify certain molecular alterations that might serve as targets for new diagnostic tools and disease-specific therapy.Chronic pancreatitis (CP) is a long-lasting inflammatory disease of the pancreas characterized by irreversible and progressive destruction of the whole organ, resulting in severe exocrine and endocrine insufficiency.1,2 Heavy alcohol consumption is the main etiologic factor in Western industrialized countries.2-4 However, less common causes, including nutritional factors, gene mutations (hereditary CP), metabolic disturbances, congenital anomalies of the ductal system (pancreas divisum), and acquired pancreatic duct obstructions, have also been shown to be etiologic factors in CP. 2,3,5,6 Despite our better understanding and characterization of the underlying etiology in recent years, in approximately 15% of the patients the etiology of CP is unknown (idiopathic CP). 4,7 The morphologic changes of CP are well described by histopathologic analysis. They include acinar cell degeneration, dilatation of the duct system with or without intraductal protein plugs and stones, necrosis, and replacement Correspondence: Helmut Friess, MD,

Transcriptional network governing the angiogenic switch in human pancreatic cancer

“…All studies were approved by the ethics committees of the University of Bern (Bern, Switzerland) and the University of Heidelberg, and written informed consent was obtained from all patients. Human tissue samples and RNA were processed as described (58). Total RNA from HDMVEC was isolated by using the RNeasy Kit (Qiagen, Hilden, Germany).…”

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Association of Cysteine-Rich Secretory Protein 3 and β-Microseminoprotein with Outcome after Radical Prostatectomy

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