Gene expression profiles of pancreatic cancer and stromal desmoplasia.
Gene expression studies were undertaken in normal pancreas and pancreatic adenocarcinomas to determine new candidate genes that can potentially be used as markers of the disease. The characteristic desmoplastic stromal reaction of pancreatic adenocarcinoma greatly hampers expression studies in this tumour type, and usually necessitates time-consuming tissue microdissection for enrichment of the tumour cell population. We show that fine needle aspiration of cancer provides a fast and efficient way of obtaining samples highly enriched in tumour cells with sufficient yields of RNA. Using Atlas cancer cDNA arrays with 588 cancer-related genes, we describe gene expression profiles of normal pancreas, bulk pancreatic tumour tissues and pancreatic tumour aspirates containing more than 95% tumour cells. Analysis of bulk tissue specimens revealed differentially expressed genes belonging predominantly to the stromal component of the tumour. This contrasted with the results obtained from tumour-cell enriched samples. Several genes already described in pancreatic cancer (caspase 8, TIMP1, CD9, IL-13) were also differentially expressed in our study. Furthermore, we found dysregulated expression of genes not previously associated with pancreatic adenocarcinoma, such as Rac 1, GLG1, NEDD5, RPL-13a, RPS9 and members of the Wnt5A gene family. In summary, we present a panel of genes newly identified in the pathogenesis of pancreatic adenocarcinoma and demonstrate that fine needle aspirates of the tumour mass are a convenient source of material for gene expression studies in tumours accompanied by desmoplastic reactions.
Crnogorac-Jurcevic
T
T
Imperial Cancer Research Fund Molecular Oncology Unit, Imperial College School of Medicine at Hammersmith Campus, London, UK.
Efthimiou
E
E
Capelli
P
P
Blaveri
E
E
Baron
A
A
Terris
B
B
Jones
M
M
Tyson
K
K
Bassi
C
C
Scarpa
A
A
Lemoine
N R
NR
D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001707:Biopsy, Needle; D002452:Cell Count; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D003199:Computer Systems; D058575:Decorin; D000072261:Dishevelled Proteins; D016326:Extracellular Matrix Proteins; D005355:Fibrosis; D020869:Gene Expression Profiling; D015723:Gene Library; D006801:Humans; D020407:Internet; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis / Q000235:genetics; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D017468:Receptors, Fibroblast Growth Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000096:biosynthesis / Q000235:genetics; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D020830:rac1 GTP-Binding Protein / Q000096:biosynthesis / Q000235:genetics; D000094742:Secreted Frizzled-Related Proteins
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D003094:Collagen; D058575:Decorin; D000072261:Dishevelled Proteins; D016326:Extracellular Matrix Proteins; D008565:Membrane Proteins; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D010744:Phosphoric Monoester Hydrolases; D020033:Protein Isoforms; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D012269:Ribosomal Proteins; D012795:Sialoglycoproteins; D020830:rac1 GTP-Binding Protein; C546878:DCN protein, human; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins; C086711:cysteine-rich fibroblast growth factor receptor