Combined gene expression analysis of whole-tissue and microdissected pancreatic ductal adenocarcinoma identifies genes specifically overexpressed in tumor epithelia.
OBJECTIVE
The precise details of pancreatic ductal adenocarcinoma (PDAC) pathogenesis are still insufficiently known, requiring the use of high-throughput methods. However, PDAC is especially difficult to study using microarrays due to its strong desmoplastic reaction, which involves a hyperproliferating stroma that effectively "masks" the contribution of the minoritary neoplastic epithelial cells. Thus it is not clear which of the genes that have been found differentially expressed between normal and whole tumor tissues are due to the tumor epithelia and which simply reflect the differences in cellular composition. To address this problem, laser microdissection studies have been performed, but these have to deal with much smaller tissue sample quantities and therefore have significantly higher experimental noise.


METHODS
In this paper we combine our own large sample whole-tissue study with a previously published smaller sample microdissection study by Grützmann et al. to identify the genes that are specifically overexpressed in PDAC tumor epithelia.


RESULTS
The overlap of this list of genes with other microarray studies of pancreatic cancer as well as with the published literature is impressive. Moreover, we find a number of genes whose over-expression appears to be inversely correlated with patient survival: keratin 7, laminin gamma 2, stratifin, platelet phosphofructokinase, annexin A2, MAP4K4 and OACT2 (MBOAT2), which are all specifically upregulated in the neoplastic epithelia, rather than the tumor stroma.


CONCLUSIONS
We improve on other microarray studies of PDAC by putting together the higher statistical power due to a larger number of samples with information about cell-type specific expression and patient survival.
Badea
Liviu
L
Bioinformatics Group, National Institute for Research in Informatics, Bucharest 011455, Romania. badea.liviu@gmail.com
Herlea
Vlad
V
Dima
Simona Olimpia
SO
Dumitrascu
Traian
T
Popescu
Irinel
I
D048948:14-3-3 Proteins; D000230:Adenocarcinoma / Q000235:genetics*; D017306:Annexin A2 / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D005092:Exonucleases / Q000378:metabolism; D005095:Exoribonucleases; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D053552:Keratin-7 / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D042282:Microdissection; D009363:Neoplasm Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010190:Pancreatic Neoplasms / Q000235:genetics*; D025221:Phosphofructokinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism
D048948:14-3-3 Proteins; D017306:Annexin A2; D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; C507497:KRT7 protein, human; D053552:Keratin-7; C400567:LAMC2 protein, human; D007797:Laminin; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D025221:Phosphofructokinases; C117090:MAP4K4 protein, human; D017346:Protein Serine-Threonine Kinases; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human