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(American Journal of Pathology. 2006;168:93-103.)
© 2006 American Society for Investigative Pathology

Profiling Bladder Cancer Using Targeted Antibody Arrays

Marta Sanchez-Carbayo*, Nicholas D. Socci{dagger}, Juan Jose Lozano{ddagger}, Brian B. Haab§ and Carlos Cordon-Cardo*

From the Division of Molecular Pathology* and Computational Biology Center,{dagger} Memorial Sloan-Kettering Cancer Center, New York, New York; The Van Andel Institute,§ Grand Rapids, Michigan; and the Laboratorio de Microarrays,{ddagger} Center for Genomic Regulation, Barcelona, Spain

Bladder cancer is a common malignancy requiring a high degree of surveillance because of the frequent recurrences and the poor clinical outcome of invasive disease. To date, serum biomarkers for bladder cancer lack optimal sensitivity and specificity to assist in diagnosis and disease categorization. Here, we designed antibody arrays for bladder cancer by selecting antibodies against targets differentially expressed in bladder tumors. Serum protein profiles measured by an antibody array containing 254 antibodies discriminated bladder cancer patients from controls (n = 95) with a correct classification rate of 93.7%. A second independent antibody array containing 144 antibodies revealed that protein profiles provide predictive information by stratifying patients with bladder tumors (n = 37) based on their overall survival (P = 0.0479). In addition, serum proteins, such as c-met, that were top ranked at identifying bladder cancer patients were associated with pathological stage, tumor grade, and survival when validated by immunohistochemistry of tissue microarrays containing bladder tumors (n = 173). This study provides experimental evidence for the use of several integrated technologies strengthening the process of biomarker discovery. Serum protein profiles obtained by antibody arrays represent comprehen-sive means for bladder cancer diagnosis and clinical outcome stratification, which could potentially assist in selection of cancer patients who would benefit from early, individualized therapeutic intervention.




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