title: Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity.
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.
authors.affiliation: Department of Pathology, Children's Hospital of Philadelphia, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Rebekah K
authors.initials: RK
authors.lastname: O'Donnell
authors.forename: Michael
authors.initials: M
authors.lastname: Kupferman
authors.forename: S Jack
authors.initials: SJ
authors.lastname: Wei
authors.forename: Sunil
authors.initials: S
authors.lastname: Singhal
authors.forename: Randal
authors.initials: R
authors.lastname: Weber
authors.forename: Bert
authors.initials: B
authors.lastname: O'Malley
authors.forename: Yi
authors.initials: Y
authors.lastname: Cheng
authors.forename: Mary
authors.initials: M
authors.lastname: Putt
authors.forename: Michael
authors.initials: M
authors.lastname: Feldman
authors.forename: Barry
authors.initials: B
authors.lastname: Ziober
authors.forename: Ruth J
authors.initials: RJ
authors.lastname: Muschel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D019718:Receptors, CXCR4