Activation of map kinase signalling via ERK5 but not ERK1 expression is associated with lymph node metastases in oral squamous cell carcinoma (OSCC)

Carsten Sticht, Kolja Freier, Karl Knöpfle, Christa Flechtenmacher, Susanne Pungs, Hofele M Christof, Meinhard Hahn, Stefan Joos and Peter Lichter

Year 2008, Volume 10, Issue 5

Abstract

In an attempt to further elucidate the pathomechanisms in oral squamous cell carcinoma (OSCC), gene expression profiling using a whole-transcriptome chip that contains 35,035 gene-specific 70mere oligonucleotides (Human Oligoset 4.0; Operon) to a set of 35 primary OSCCs. Altogether, 7390 genes were found differentially expressed between OSCC tumor samples and oral mucosa. To characterize the major biological processes in this tumor collection, MAPPFinder, a component of GenMAPP version 2.1, was applied to this data set to generate a statistically ranked list of molecular signalling pathways. Among others, cancer-related pathways like MAP kinase signalling (z-score=4.6, p<0.001), TGF-beta signalling (z-score=3.0, p=0.015) and signalling pathways involved in apoptosis (z-score=2.1, p=0.037), were found de-regulated in the OSCC collection analyzed. Focussing on the MAP kinase signalling pathway, subsequent tissue microarray (TMA) analyses by immunohistochemistry revealed an increase in protein expression of MAP kinase-related proteins ERK1 in 22.8% (48/209) and ERK5 in 27.4% (76/277), respectively. An association of high ERK5 but not of high ERK1 expression with advanced tumor stage and the presence of lymph node metastases was found (p=0.008 and p=0.016, respectively). Our analysis demonstrates the reliability oft the combined approach of gene expression profiling, signalling pathway analyses and tissue microarray analysis to detect novel distinct molecular aberrations in OSCC.

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