Analysis of paired primary lung and lymph node tumor cells: A model of metastatic potential by multiple genetic programs

Chuong D. Hoang, Tenner J. Guillaume, Sean C. Engel, Sherif H. Tawfic, Robert A Kratzke, Michael A Maddaus

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Background: The current paradigm of metastasis proposes that rare cells within primary tumors acquire metastatic capability via sequential mutations, suggesting that metastases are genetically dissimilar from their primary tumors. We tested this hypothesis by examining the molecular differences, if any, between primary tumor cells and matched lymph node metastatic cells in human non-small-cell lung carcinoma specimens. Methods: We performed transcriptional profiling studies on malignant cells from 11 pairs of stage III tumors and their tumor-positive lymph nodes using multiple, complementary analytic techniques. To confirm the overall validity of microarray data, we used real-time polymerase chain reaction. Results: The molecular signature of nodal metastasis was a composite of two paradoxical, but not mutually exclusive, expression patterns: metastatic cells are: (1) different from their primary tumor cells based on a few genes and (2) genetically similar, overall, to their primary tumor cells. Consequently, we found a 27-gene subset sufficient to differentiate nodal metastatic cells from primary tumor cells. Conclusions: Thus, we concluded that a more accurate model of metastatic potential is based on a global primary tumor expression pattern along with the appearance of distinct metastatic variants. The 27-gene signature differentiating primary tumors from their metastatic cells may define non-small-cell lung carcinoma nodal metastatic potential.

Original languageEnglish (US)
Pages (from-to)509-517
Number of pages9
JournalCancer Detection and Prevention
Volume29
Issue number6
DOIs
StatePublished - 2005

Keywords

  • Expression profiling
  • Hierarchical clustering
  • Laser capture microdissection
  • Lymph node metastatic cells
  • Metastasis
  • Metastatic potential
  • Microarray
  • Model
  • NSCLC
  • Non-small-cell lung carcinoma
  • RNA isolation
  • Real-time quantitative RT-PCR

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