title: Identification of 14-3-3 theta as an antigen that induces a humoral response in lung cancer.
abstract: We have implemented a strategy to identify tumor antigens that induce a humoral immune response in lung cancer based on the analysis of tumor cell proteins. Chromatographically fractionated protein extracts from three lung cancer cell lines were subjected to Western blotting and hybridization with individual sera to determine serum antibody binding. Two sets of sera were initially investigated. One set consisted of sera from 19 newly diagnosed subjects with lung adenocarcinoma and 19 matched controls. A second independent set consisted of sera from 26 newly diagnosed subjects with lung adenocarcinoma and 24 controls matched for age, gender, and smoking history. One protein that exhibited significant reactivity with both sets of cancer sera (P = 0.0008) was confidently identified by mass spectrometry as 14-3-3 theta. Remarkably, significant autoantibody reactivity against 14-3-3 theta was also observed in an analysis of a third set consisting of 18 prediagnostic lung cancer sera collected as part of the Beta-Carotene and Retinol Efficacy Trial cohort study, relative to 19 matched controls (P = 0.0042). A receiver operating characteristic curve constructed with a panel of three proteins consisting of 14-3-3 theta identified in this study, plus annexin 1 and protein gene product 9.5 proteins previously identified as associated with autoantibodies in lung cancer, gave a sensitivity of 55% at 95% specificity (area under the curve, 0.838) in discriminating lung cancer at the preclinical stage from matched controls.
authors: Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors: Sandra R
authors: SR
authors: Pereira-Faca
authors: Rork
authors: R
authors: Kuick
authors: Eric
authors: E
authors: Puravs
authors: Qing
authors: Q
authors: Zhang
authors: Alexei L
authors: AL
authors: Krasnoselsky
authors: Douglas
authors: D
authors: Phanstiel
authors: Ji
authors: J
authors: Qiu
authors: David E
authors: DE
authors: Misek
authors: Robert
authors: R
authors: Hinderer
authors: Martin
authors: M
authors: Tammemagi
authors: Maria Teresa
authors: MT
authors: Landi
authors: Neil
authors: N
authors: Caporaso
authors: Ruth
authors: R
authors: Pfeiffer
authors: Cim
authors: C
authors: Edelstein
authors: Gary
authors: G
authors: Goodman
authors: Matt
authors: M
authors: Barnett
authors: Mark
authors: M
authors: Thornquist
authors: Dean
authors: D
authors: Brenner
authors: Samir M
authors: SM
authors: Hanash
mesh_terms: D048948:14-3-3 Proteins / Q000032:analysis* / Q000737:chemistry / Q000276:immunology; D000230:Adenocarcinoma / Q000276:immunology*; D000917:Antibody Formation; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D001323:Autoantibodies / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis* / Q000737:chemistry; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000737:chemistry / Q000276:immunology; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology*; D013058:Mass Spectrometry; D012016:Reference Values
chemical_list: D048948:14-3-3 Proteins; D000951:Antigens, Neoplasm; D001323:Autoantibodies; D015415:Biomarkers; D014408:Biomarkers, Tumor