title: Survivin Autoantibodies Are Not Elevated in Lung Cancer When Assayed Controlling for Specificity and Smoking Status.
abstract: The high mortality rate in lung cancer is largely attributable to late diagnosis. Case-control studies suggest that autoantibodies to the survivin protein are potential biomarkers for early diagnosis. We tested the hypothesis that sandwich ELISA can detect autoantibodies to survivin before radiologic diagnosis in patients with early-stage non-small cell lung cancer (NSCLC). Because previous studies assayed survivin autoantibodies with the direct antigen-coating ELISA (DAC-ELISA), we first compared that assay with the sandwich ELISA. Based on the more robust results from the sandwich ELISA, we used it to measure survivin autoantibodies in the serum of 100 individuals from a well-controlled population study [the Dutch-Belgian Lung Cancer Screening Trial (NELSON) trial] composed of current and former smokers (50 patients with NSCLC, both before and after diagnosis, and 50 matched, smoking-habit control subjects), and another 50 healthy nonsmoking control subjects. We found no difference in specific autoantibodies to survivin in NSCLC patients, although nonspecific median optical densities were 24% higher (P < 0.001) in both NSCLC patients and smokers, than in healthy nonsmokers. Finally, we confirmed the ELISA results with Western blot analysis of recombinant and endogenous survivin (HEK-293), which showed no anti-survivin reactivity in patient sera. We conclude that specific anti-survivin autoantibody reactivity is most likely not present in sera before or after diagnosis. Autoantibody studies benefit from a comparison to a well-controlled population, stratified for smoking habit.
authors.affiliation: Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Broodman
authors.affiliation: Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Martijn M
authors.initials: MM
authors.lastname: VanDuijn
authors.affiliation: Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Christoph
authors.initials: C
authors.lastname: Stingl
authors.affiliation: Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Lennard J M
authors.initials: LJ
authors.lastname: Dekker
authors.affiliation: Department of Immunology and Histocompatibility, School of Medicine, University of Thessaly, Larissa, Greece.
authors.forename: Anastasios E
authors.initials: AE
authors.lastname: Germenis
authors.affiliation: Unit of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Harry J
authors.initials: HJ
authors.lastname: de Koning
authors.affiliation: Department of Pulmonology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: van Klaveren
authors.affiliation: Department of Pulmonology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Joachim G
authors.initials: JG
authors.lastname: Aerts
authors.affiliation: Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Lindemans
authors.affiliation: Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands. t.luider@erasmusmc.nl.
authors.forename: Theo M
authors.initials: TM
authors.lastname: Luider
mesh_terms: D000368:Aged; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D014408:Biomarkers, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000276:immunology*; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012907:Smoking; D000077022:Survivin
chemical_list: D001323:Autoantibodies; C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin