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Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity

Oncogene volume 24, pages 1244–1251 (2005)Cite this article

Abstract

Metastasis via the lymphatics is a major risk factor in squamous cell carcinoma of the oral cavity (OSCC). We sought to determine whether the presence of metastasis in the regional lymph node could be predicted by a gene expression signature of the primary tumor. A total of 18 OSCCs were characterized for gene expression by hybridizing RNA to Affymetrix U133A gene chips. Genes with differential expression were identified using a permutation technique and verified by quantitative RT–PCR and immunohistochemistry. A predictive rule was built using a support vector machine, and the accuracy of the rule was evaluated using crossvalidation on the original data set and prediction of an independent set of four patients. Metastatic primary tumors could be differentiated from nonmetastatic primary tumors by a signature gene set of 116 genes. This signature gene set correctly predicted the four independent patients as well as associating five lymph node metastases from the original patient set with the metastatic primary tumor group. We concluded that lymph node metastasis could be predicted by gene expression profiles of primary oral cavity squamous cell carcinomas. The presence of a gene expression signature for lymph node metastasis indicates that clinical testing to assess risk for lymph node metastasis should be possible.

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Acknowledgements

We thank Amy Ziober for RNA preparation of the validation patient set, Jim O’Donnell for development of JScatter, the Greater Philadelphia Bioinformatics Alliance and the Institute for Genomics Research for presenting the Microarray Data Analysis Workshop, and the University of Pennsylvania Microarray Core Facility for chip processing and consultation.

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Author notes

  1. Rebekah K O'Donnell and Michael Kupferman: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Pathology, Children's Hospital of Philadelphia, Hospital of the University of Pennsylvania, Philadelphia, PA, USA

    Rebekah K O'Donnell, Yi Cheng & Ruth J Muschel

  2. Department of Otorhinolaryngology–Head and Neck Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA

    Michael Kupferman, Randal Weber, Bert O'Malley Jr & Barry Ziober

  3. Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA

    S Jack Wei

  4. Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA

    Michael Feldman

  5. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Sunil Singhal

  6. Department of Biostatistics and Epidemiology, University of Pennsylvania, PA, USA

    Mary Putt

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  1. Rebekah K O'Donnell
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  2. Michael Kupferman
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Correspondence to Ruth J Muschel.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc).

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O'Donnell, R., Kupferman, M., Wei, S. et al. Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity. Oncogene 24, 1244–1251 (2005). https://doi.org/10.1038/sj.onc.1208285

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