Vergleich der publizierten Genexpressionsdaten beim Pankreaskarzinom
Art des Experiments: Meta-Analyse
Studienziel: Vergleich der publizierten Genexpressionsdaten beim Pankreaskarzinom
Software: Excel
Kriterien für die von Kanditatengenen: Differentielle Expression in mindestens
zwei Experimenten verschiedener Arbeitsgruppen Ergebnisse: During the last years
microarray analysis has become a standard technique to identify genes differentially
expressed in various tumour entities. Up till now seven papers showing an aberrant
gene expression profile in pancreatic cancer have been published. Comparing
these data and our own results, we surveyed a total number of 548 differentially
expressed genes. We found 86 genes described to be differentially expressed
in more than one study. The majority of these genes (n=70) were found to be
upregulated in pancreatic cancer, whereas 16 were revealed to be downregulated.
Only a single gene, i.e. S100 calcium binding protein P, was described to be
upregulated in five out of the eight studies. Four genes, among them integrin
beta4, were found to be over expressed in four studies. Three studies corresponded
in describing a group of nineteen genes as over expressed. Revealing the conformity
in two studies a set of forty-six genes was upregulated. Comparing these recent
microarray data with previous publications overall 9 genes, including Stratifin
and CD55, have been implicated in pancreatic cancer before. These examples may
support the validity of microarray-based expression profiling. In addition 14
of the upregulated genes in pancreatic cancer are known to be involved in other
tumour entities. The remaining candidates have not been implicated in carcinogenesis
yet. Striking discrepancies in these studies were restricted to only one gene,
i.e. NAP1L1. There are several potential reasons for the overall rather low
concordance of these studies: the type, histology and number of investigated
samples differed considerably (i). Microdissection was applied in the study
of our group only (ii). Different types of arrays and hybridisation technologies
may cause different results (iii). There is no standardised procedure for statistical
analysis and data mining (iv). Taken together, the results of expression profiling
studies in pancreatic adenocarcinoma are not yet really comparable. This fosters
the need of further verification steps investigating the differentially expressed
candidate genes by independent methods such as real time RT-PCR. Furthermore,
the validation must extend the efforts to protein level using immunohistochemistry
or Western blotting procedures.