Molecular alterations in pancreatic carcinoma: expression profiling shows that dysregulated expression of S100 genes is highly prevalent.
In order to expand our understanding of the molecular changes underlying the complex pathology of pancreatic malignancy, global gene expression profiling of pancreatic adenocarcinoma compared with normal pancreatic tissue was performed. Human cDNA arrays comprising 9932 elements were interrogated with fluorescence-labelled normal and adenocarcinoma samples (nine tumours, three normal pancreata, and three cell lines). The data were analysed for differential gene expression, which was confirmed by serial analysis of gene expression (SAGE), digital differential display (DDD) analysis, and immunohistochemistry for selected cases. The array data were filtered to produce lists of a total of 75 genes significantly up-regulated or down-regulated in pancreatic adenocarcinoma. Two of those showing the highest differential were members of the S100 family of Ca-binding proteins, namely S100P and S100A6, and therefore the S100 genes were studied in more detail. By immunohistochemical analysis of custom-built, pancreas-specific tissue arrays and commercially available, normal/cancer tissue arrays that included a wide variety of different tumour types, differential expression of S100P protein was found to be almost exclusive to pancreatic cancer. S100P could therefore represent a useful biomarker for pancreatic adenocarcinomas.
Crnogorac-Jurcevic
Tatjana
T
Cancer Research UK Molecular Oncology Unit, Imperial College London Faculty of Medicine at Hammersmith Campus, London W12 0NN, UK. tatjana.jurcevic@cancer.org.uk
Missiaglia
Edoardo
E
Blaveri
Ekaterina
E
Gangeswaran
Rathi
R
Jones
Melanie
M
Terris
Benoit
B
Costello
Eithne
E
Neoptolemos
John P
JP
Lemoine
Nicholas R
NR
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics; D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; C103003:S100P protein, human; C055351:S100A6 protein, human