The pancreatic cancer study sought to establish a transcriptional signature of tumour versus normal pan creatic tissue by laser capture of cancerous and normal tis sue from the same pancreas. In total 39 sample pairs were published and we find a high positive correlation with the http://www.selleckchem.com/products/Dasatinib.html corticosteroid resistance profile, p 2 10 6 and a K S significance score of p 3 10 7. The enrichment curve is shown in Figure 4C. In this context it has been reported that loss of GR expression has been seen in pancreatic car cinoma relative to normal tissue and elevating GR expression has been shown to inhibit pancreatic tumour growth in a hamster model. The query results are given in the additional file 2. Neurodegenerative Disease The analysis of gene expression changes associated with neurodegenerative disease has been hampered by the difficulty of extracting high quality RNA from post mor tem tissue.
One way of validating a disease asso ciated gene expression profile is to show that it shares significant features with profiles derived from indepen dent experiments on related pathologies. A positive result would validate the query profile and furthermore lead to a more robust core response profile based on multiple experiments. To this end we constructed three separate query profiles based on transcriptional profiles from the brains of patients with three degrees of severity of Alzhei mers disease, see additional file 1. The number of significant changes increases with severity of disease and we queried the SPIED with these three profiles, see additional file 2.
Not surprisingly, the high scoring corre lations are those from which the query profiles were derived. In addition to these the query returned correla tions with other AD studies and various neurodegenera tive diseases. The high scoring AD expression series was an extensive study of 161 samples from various brain regions of AD patients and age matched controls. Ignoring brain regions for now, there are 87 AD samples and 74 controls. Ranking the samples according to corre lation score against the severe AD query profile we find a very significant enrichment of positive correlations with AD samples. Pooling the samples from the different brain regions results in significant correlations for 5 out of the 6 brain regions, see Figure 5.
In addition to AD correlations we found high scoring correlations with samples derived from Huntingtons disease, Downs syndrome, Parkinsons dis ease and bipolar disorder brains. In this sense the profile cannot be considered to distinguish AD pathology from other degenerative diseases. Drug_discovery However, it is of interest to examine in greater detail these cross dis ease similarities. In particular, the severe AD query had a high correlation with severe stage HD caudate nucleus samples. The HD study consisted of 404 samples split across two platforms in three brain regions from control and HD individuals. The high correlation was with the GPL96 series.