Identification of disease-specific genes in chronic pancreatitis using DNA array technology.
OBJECTIVE
To use DNA arrays to analyze the differential gene expression patterns in the normal pancreas and in pancreatic diseases.


BACKGROUND
Genome-wide gene expression analysis will provide new insights into gene function and cause of disease.


METHODS
RNA was extracted from eight normal pancreatic specimens, eight specimens with chronic pancreatitis (CP), and eight pancreatic cancer (PCa) tissues. Poly A(+) RNA was purified, reverse-transcribed, and converted into cRNA using biotinylated nucleotides. The HuGeneFL DNA array containing 5,600 full-length human genes was used for analysis.


RESULTS
First, 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.


CONCLUSIONS
The 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.
Friess
H
H
Department of Visceral and Transplantation Surgery, Inselspital, University of Bern, Bern, Switzerland. helmut_friess@med.uni-heidelberg.de
Ding
J
J
Kleeff
J
J
Liao
Q
Q
Berberat
P O
PO
Hammer
J
J
Büchler
M W
MW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015152:Blotting, Northern; D064236:Cartilage Oligomeric Matrix Protein; D002908:Chronic Disease; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015321:Gene Rearrangement; D006023:Glycoproteins / Q000032:analysis / Q000235:genetics; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000032:analysis / Q000235:genetics; D008297:Male; D064235:Matrilin Proteins; D008875:Middle Aged; D009077:Mucins / Q000032:analysis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010179:Pancreas / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000235:genetics; D010195:Pancreatitis / Q000235:genetics*; D012471:Salivary Proteins and Peptides / Q000032:analysis / Q000235:genetics; D029589:Seminal Plasma Proteins / Q000032:analysis / Q000235:genetics; D012697:Serine Endopeptidases / Q000032:analysis / Q000235:genetics; D053802:Tryptases
C489926:CRISP3 protein, human; D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D007146:Immunoglobulin lambda-Chains; D064235:Matrilin Proteins; D009077:Mucins; D012471:Salivary Proteins and Peptides; D029589:Seminal Plasma Proteins; C577553:TSP5 protein, human; D012697:Serine Endopeptidases; D053802:Tryptases