Profiling bladder cancer using targeted antibody arrays.
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 comprehensive 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.
Sanchez-Carbayo
Marta
M
Division of Molecular Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. Marta.Sanchez-Carbayo@cnio.es
Socci
Nicholas D
ND
Lozano
Juan Jose
JJ
Haab
Brian B
BB
Cordon-Cardo
Carlos
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies; D014408:Biomarkers, Tumor / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D040081:Protein Array Analysis / Q000379:methods; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D046888:Tissue Array Analysis; D001749:Urinary Bladder Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000401:mortality
D000906:Antibodies; D014408:Biomarkers, Tumor