Article Text

  1. V. Ramiah1,
  2. A. Potti1,
  3. H. Dressman1,
  4. D. Harpole1,
  5. T. L. Ortel1
  1. 1Duke University, Durham, NC


Background Venous thromboembolism (VTE) is the leading cause of death in patients with cancer. The 1-year survival rate in patients diagnosed with cancer at the time of VTE is 12% compared with 36% in cancer patients who are free of thrombosis. VTE in cancer patients may indicate a more aggressive phenotype.

Methods With the overarching goal of testing, the ability of gene expression profiling to detect biologically and clinically significant differences in patients with cancer and VTE, using non-small cell lung cancer (NSCLC) as a proof of principle, we have expanded on previous work wherein we have shown the ability of multiple gene expression patterns (‘metagenes’) to predict a thrombotic event (Potti A. Blood 2005). Ninety-six patients with NSCLC were enrolled in this study. RNA was extracted and gene array data obtained using an Affymetrix U133 2.0 plus GeneChip. The clinical history of all 96 patients was reviewed to identify those patients with a definitive VTE episode soon after the initial diagnosis of cancer and not within 6 weeks of surgery. Fourteen of ninety-six96 (14.5%) patients met these criteria. We then identified 14 additional patients with NSCLC matched by age, gender, and clinical stage patients who did not have VTE for at least 2 years following the diagnosis of cancer. Gene expression data were analyzed using a binary regression analysis.

Results Using the metagene approach, a discriminator gene set (n = 50) that differentiated patients with NSCLC and VTE from patients with NSCLC without VTE was identified. A leave-one-out cross-validation performed to further assess the reliability of the discriminator metagene set was greater than 85% accurate in identifying patients with NSCLC and VTE. Also, significant biologically relevant differences were seen between the comparison groups, to include genes such as P53, VEGFC, E2F4, TFPI, and EPHB2.

Conclusions Our data suggest that a genomic approach can be used to identify and characterize patients with NSCLC that develop VTE, while also providing information important to an understanding of the underlying biology of the association between cancer and thrombosis.

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