title: Activation of MAP kinase signaling through ERK5 but not ERK1 expression is associated with lymph node metastases in oral squamous cell carcinoma (OSCC).
abstract: In an attempt to further elucidate the pathomechanisms in oral squamous cell carcinoma (OSCC), gene expression profiling was performed using a whole-transcriptome chip that contains 35,035 gene-specific 70 mere oligonucleotides (Human OligoSet 4.0; Operon, Cologne, Germany) 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 biologic 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 signaling pathways. Among others, cancer-related pathways, such as mitogen-activated protein (MAP) kinase signaling (z score = 4.6, P < .001), transforming growth factor-beta signaling (z score = 3.0, P = .015), and signaling pathways involved in apoptosis (z score = 2.1, P = .037), were found deregulated in the OSCC collection analyzed. Focusing on the MAP kinase signaling pathway, subsequent tissue microarray analyses by immunohistochemistry revealed an increase in protein expression of MAP kinase-related proteins ERK1 in 22.8% (48 of 209) and ERK5 in 27.4% (76 of 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 = .008 and P = .016, respectively). Our analysis demonstrates the reliability of the combined approach of gene expression profiling, signaling pathway analyses, and tissue microarray analysis to detect novel distinct molecular aberrations in OSCC.
authors.affiliation: Abteilung Molekulare Genetik (B060), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Sticht
authors.forename: Kolja
authors.initials: K
authors.lastname: Freier
authors.forename: Karl
authors.initials: K
authors.lastname: Knöpfle
authors.forename: Christa
authors.initials: C
authors.lastname: Flechtenmacher
authors.forename: Susanne
authors.initials: S
authors.lastname: Pungs
authors.forename: Christof
authors.initials: C
authors.lastname: Hofele
authors.forename: Meinhard
authors.initials: M
authors.lastname: Hahn
authors.forename: Stefan
authors.initials: S
authors.lastname: Joos
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D004789:Enzyme Activation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009061:Mouth Mucosa / Q000378:metabolism* / Q000473:pathology; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D048052:Mitogen-Activated Protein Kinase 3; D048054:Mitogen-Activated Protein Kinase 7; D020928:Mitogen-Activated Protein Kinases