Identification of metastasis-associated receptor tyrosine kinases in non-small cell lung cancer

Cancer Res. 2005 Mar 1;65(5):1778-82. doi: 10.1158/0008-5472.CAN-04-3388.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • DNA Primers / chemistry
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / metabolism
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / metabolism
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • DNA Primers
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptor Protein-Tyrosine Kinases