Profiling tumor-associated antibodies for early detection of non-small cell lung cancer

J Thorac Oncol. 2006 Jul;1(6):513-9.

Abstract

Background: A blood test for non-small cell lung cancer (NSCLC) may be a valuable tool for use in a comprehensive lung cancer screening strategy. Here we report the potential of autoantibody profiling to detect early-stage and occult NSCLC.

Methods: T7-phage NSCLC cDNA libraries were screened with patient plasma to identify phage-expressed proteins recognized by tumor-associated antibodies. Two hundred twelve immunogenic phage-expressed proteins, identified from 4000 clones, were statistically ranked for their individual reactivity with 23 stage I cancer patient and 23 risk-matched control samples. All 46 samples were used as a training set to define a combination of markers that were best able to distinguish patient from control samples; this set of classifiers was then examined using leave-one-out cross-validation. Markers were then used to predict probability of disease in 102 samples from the Mayo Clinic CT Screening Trial (six prevalence cancer samples, 40 drawn 1 to 5 years before diagnosis, and 56 risk-matched controls).

Results: Measurements of the five most predictive antibody markers in 46 cases and controls were combined in a logistic regression model that yielded area under the receiver operating characteristics curve of 0.99; leave-one-out validation achieved 91.3% sensitivity and 91.3% specificity. In testing this marker set with samples from the Mayo Clinic Lung Screening Trial, we correctly predicted six of six prevalence cancers, 32 of 40 cancers from samples drawn 1 to 5 years before radiographic detection on incidence screening, and 49 of 56 risk-matched controls.

Conclusions: Antibody profiling may be a useful tool for early detection of NSCLC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Neoplasm / blood
  • Antibodies, Neoplasm / immunology*
  • Bacteriophage T7 / genetics
  • Biomarkers, Tumor / blood
  • Carcinoma, Non-Small-Cell Lung / epidemiology*
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Case-Control Studies
  • Cohort Studies
  • Early Diagnosis
  • Female
  • Gene Library
  • Humans
  • Incidence
  • Logistic Models
  • Lung Neoplasms / epidemiology*
  • Lung Neoplasms / immunology*
  • Male
  • Mass Screening / methods*
  • Middle Aged
  • Neoplasm Staging
  • Predictive Value of Tests
  • Protein Array Analysis
  • ROC Curve
  • Reference Values
  • Sensitivity and Specificity

Substances

  • Antibodies, Neoplasm
  • Biomarkers, Tumor