title: Genetic variant as a selection marker for anti-prostate stem cell antigen immunotherapy of bladder cancer.
abstract: A monoclonal antibody against prostate stem cell antigen (PSCA) has emerged as a novel cancer therapy currently being tested in clinical trials for prostate and pancreatic cancers, but this treatment is likely to be efficient only in patients with PSCA-expressing tumors. The present study demonstrates that a genetic variant (rs2294008) discovered by bladder cancer genome-wide association studies is a strong predictor of PSCA protein expression in bladder tumors, as measured by two-sided multivariable linear regression (P = 6.46×10(-11); n = 278). The association pattern is similar in non-muscle-invasive tumors, stages Ta (P = 3.10×10(-5); n = 173) and T1 (P = 2.64×10(-5); n = 60), and muscle-invasive tumors, stages T2 (P =.01; n = 23) and T3/4 (P =.03; n = 22). The study suggests that anti-PSCA immunotherapy might be beneficial for bladder cancer patients with high tumor PSCA expression, which is statistically significantly associated with the presence of CT and TT genotypes of a common genetic variant, rs2294008. Future clinical studies will be needed to validate PSCA as a therapeutic target for bladder cancer.
authors.affiliation: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 8717 Grovemont Cir, Bethesda, MD 20892-4605, USA.
authors.forename: Indu
authors.initials: I
authors.lastname: Kohaar
authors.forename: Patricia
authors.initials: P
authors.lastname: Porter-Gill
authors.forename: Petra
authors.initials: P
authors.lastname: Lenz
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Fu
authors.forename: Adam
authors.initials: A
authors.lastname: Mumy
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Apolo
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Dalsu
authors.initials: D
authors.lastname: Baris
authors.forename: Alan R
authors.initials: AR
authors.lastname: Schned
authors.forename: Kris
authors.initials: K
authors.lastname: Ylaya
authors.forename: Molly
authors.initials: M
authors.lastname: Schwenn
authors.forename: Alison
authors.initials: A
authors.lastname: Johnson
authors.forename: Michael
authors.initials: M
authors.lastname: Jones
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kida
authors.forename: Debra T
authors.initials: DT
authors.lastname: Silverman
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
authors.forename: Lee E
authors.initials: LE
authors.lastname: Moore
authors.forename: Ludmila
authors.initials: L
authors.lastname: Prokunina-Olsson
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000276:immunology*; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods*; D016014:Linear Models; D008297:Male; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology*; D011237:Predictive Value of Tests; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000628:therapy*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human