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 radiological diagnosis in early-stage non-small-cell lung cancer (NSCLC) patients. 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 controls), and another 50 healthy non-smoking controls. We found no difference in specific autoantibodies to survivin in NSCLC patients, although non-specific median optical densities (ODs) were 24% higher (p<0.001) in both NSCLC patients and smokers, than in healthy non-smokers. 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.
- Received October 18, 2014.
- Revision received September 25, 2015.
- Accepted September 25, 2015.
- Copyright © 2015, American Association for Cancer Research.