Novel markers of subclinical disease for Ewing family tumors from gene expression profiling Journal Article


Authors: Cheung, I. Y.; Feng, Y.; Danis, K.; Shukla, N.; Meyers, P.; Ladanyi, M.; Cheung, N. K. V.
Article Title: Novel markers of subclinical disease for Ewing family tumors from gene expression profiling
Abstract: Purpose: Targeting subclinical disease in the bone marrow is particularly relevant in metastatic Ewing family tumors (EFT) where cure is difficult. Genome-wide expression arrays can uncover novel genes differentially expressed in tumors over normal marrow/blood, which may have potentials as markers of subclinical disease. Experimental Design: Gene expression array data were obtained on 28 EFT tumors using the Affymetrix U133 gene chip and compared with 10 normal blood samples. Ten genes with high tumor to blood ratios were identified. Quantitative reverse transcription-PCR was done to study (a) the dynamic range of detection of rare tumor cells, (b) the gene expression in normal blood/marrow samples, (c) the gene expression among EFT tumors, and (d) the detection and prognostic impact of marker positivity in histology-negative diagnostic marrows of EFT patients. Results: Five of 10 genes (i.e., six-transmembrane epithelial antigen of the prostate 1 [STEAP1], cyclin D1 [CCND1], NKX2-2 transcription factor [NKX2-2], plakophilin 1 [PKP1], and transmembrane protein 47 [TMEM47]) were chosen for further analyses based on their steep linear dynamic range in detecting tumor cells seeded in normal mononuclear cells and on their homogeneous expression among EFT tumors. Prognostic effect was evaluated in 35 histology-negative diagnostic marrows. Marker negativity of STEAP1, CCND1, or NKX2-2, as well as three markers in combination, was strongly correlated with patient survival as well as survival without new metastases. Conclusions: This gene expression array-based approach identified novel markers that may be informative at diagnosis for risk group assessment. Their clinical utility needs to be tested in large patient cohorts. © 2007 American Association for Cancer Research.
Keywords: adolescent; cancer survival; controlled study; human tissue; retrospective studies; unclassified drug; human cell; cancer risk; cancer patient; cancer diagnosis; sensitivity and specificity; biological marker; metastasis; reverse transcription polymerase chain reaction; cohort studies; gene expression profiling; bone marrow; tumor markers, biological; protein; cell line, tumor; ewing sarcoma; kaplan-meiers estimate; mononuclear cell; blood sampling; diagnostic value; reverse transcriptase polymerase chain reaction; microarray analysis; oligonucleotide array sequence analysis; device; membrane protein; tumor cell; oncogene proteins, fusion; high risk population; cyclin d1; sarcoma, ewing's; proto-oncogene protein c-fli-1; tau protein; chondroitin sulfate proteoglycan 5; fat tumor suppressor homologue 4 protein; fibronectin leucine rich transmembrane protein 2; plakophilin 1; proteochondroitin sulfate; six transmembrane epithelial antigen of the prostate 1; transcription factor nkx2 2; transmembrane protein 47; wingless related mmtv integration site 5a protein
Journal Title: Clinical Cancer Research
Volume: 13
Issue: 23
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2007-12-01
Start Page: 6978
End Page: 6983
Language: English
DOI: 10.1158/1078-0432.ccr-07-1417
PUBMED: 18056173
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 14" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Nai-Kong Cheung
    439 Cheung
  2. Marc Ladanyi
    861 Ladanyi
  3. Irene Y Cheung
    73 Cheung
  4. Paul Meyers
    242 Meyers
  5. Neerav Shukla
    69 Shukla
  6. Yi Feng
    5 Feng
  7. Karen E Danis
    6 Danis