title: Identification of metastasis-associated receptor tyrosine kinases in non-small cell lung cancer.
abstract: Development of distant metastasis after tumor resection is the leading cause of death in early-stage non-small cell lung cancer (NSCLC). Receptor tyrosine kinases (RTK) are involved in tumorigenesis but only few RTKs have been systematically studied in NSCLC. Here, we provide quantitative real-time reverse transcription-PCR expression data of all RTKs (n=56) in primary tumors of 70 patients with early-stage (I-IIIA) NSCLC. Overall, 33 RTKs were expressed in at least 25% of the patients. Several RTKs were significantly expressed higher in tumors that ultimately metastasized. The hazard risk for metastasis development in stage I/II disease was increased at least 3-fold for tumors with high expression levels of insulin receptor, neurotrophic tyrosine receptor kinase 1, epidermal growth factor receptor, ERBB2, ERBB3, platelet-derived growth factor receptor beta, fibroblast growth factor receptor 1, or leukocyte tyrosine kinase. Relative risks were reduced 3-fold by expression of EPHB6 or DKFZ1. Three members of the epidermal growth factor receptor family were associated with a high risk of metastasis, emphasizing the validity of our data. High ERBB3 expression was significantly associated with decreased survival. Taken together, our genome-wide RTK expression map uncovered the previously unknown value of several RTKs as potential markers for prognosis and metastasis prediction in early-stage NSCLC. The identified RTKs represent promising novel candidates for further functional analyses.
authors.affiliation: Department of Medicine, Hematology/Oncology, University of Münster, Germany. muellerc@uni-muenster.de
authors.forename: Carsten
authors.initials: C
authors.lastname: Müller-Tidow
authors.forename: Sven
authors.initials: S
authors.lastname: Diederichs
authors.forename: Etmar
authors.initials: E
authors.lastname: Bulk
authors.forename: Thorsten
authors.initials: T
authors.lastname: Pohle
authors.forename: Björn
authors.initials: B
authors.lastname: Steffen
authors.forename: Joachim
authors.initials: J
authors.lastname: Schwäble
authors.forename: Sylvia
authors.initials: S
authors.lastname: Plewka
authors.forename: Michael
authors.initials: M
authors.lastname: Thomas
authors.forename: Ralf
authors.initials: R
authors.lastname: Metzger
authors.forename: Paul M
authors.initials: PM
authors.lastname: Schneider
authors.forename: Christian H
authors.initials: CH
authors.lastname: Brandts
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: Hubert
authors.initials: H
authors.lastname: Serve
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D020794:Receptor Protein-Tyrosine Kinases