Molecular classification of nodal metastasis in primary larynx squamous cell carcinoma

Transl Res. 2007 Oct;150(4):233-45. doi: 10.1016/j.trsl.2007.03.011. Epub 2007 May 23.

Abstract

Classification and prognosis of larynx squamous cell carcinoma (LSCC) depends on clinical and histopathological examination. Currently, expression profiling harbors the potential to investigate, classify, and better manage cancer. Gene expression profiles of 22 primary LSCCs were analyzed by microarrays containing 19,200 cDNAs. GOAL functionally classified differentially expressed genes, and a novel "in silico" procedure identified physical gene clusters differentially transcribed. A signature of 158 genes differentiated tumors with nodal metastasis. A novel statistical method allowed categorization of metastatic tumors into 2 distinct subgroups of differential gene expression patterns. Among genes correlated to nodal metastatic progression, we verified in vitro that NM23-H3 reduced cell motility and TRIM8 were a growth suppressor. Six chromosomal regions were specifically downregulated in metastatic tumors. This large-scale gene expression analysis in LSCC provides information on changes in genomic activity associated with lymphonodal metastasis and identifies molecules that might prove useful as novel therapeutic targets.

Publication types

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

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / secondary*
  • Carrier Proteins / genetics*
  • Cell Line, Tumor
  • Cluster Analysis
  • DNA, Complementary / genetics
  • Disease Progression
  • Down-Regulation / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Genes, Neoplasm
  • Humans
  • Laryngeal Neoplasms / genetics*
  • Laryngeal Neoplasms / metabolism
  • Laryngeal Neoplasms / pathology
  • Lymphatic Metastasis
  • Male
  • NM23 Nucleoside Diphosphate Kinases / genetics*
  • Neoplasm Staging
  • Nerve Tissue Proteins / genetics*
  • Oligonucleotide Array Sequence Analysis / methods
  • Prognosis
  • RNA, Neoplasm / isolation & purification
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Suppressor Proteins / genetics
  • Up-Regulation / genetics

Substances

  • Biomarkers, Tumor
  • Carrier Proteins
  • DNA, Complementary
  • NM23 Nucleoside Diphosphate Kinases
  • Nerve Tissue Proteins
  • RNA, Neoplasm
  • TRIM8 protein, human
  • Tumor Suppressor Proteins
  • NME1 protein, human