Identification of an autoantibody panel to separate lung cancer from smokers and nonsmokers

William N Rom, Judith D Goldberg, Doreen Addrizzo-Harris, Heather N Watson, Michael Khilkin, Alissa K Greenberg, David P Naidich, Bernard Crawford, Ellen Eylers, Daorong Liu, Eng M Tan, William N Rom, Judith D Goldberg, Doreen Addrizzo-Harris, Heather N Watson, Michael Khilkin, Alissa K Greenberg, David P Naidich, Bernard Crawford, Ellen Eylers, Daorong Liu, Eng M Tan

Abstract

Background: Sera from lung cancer patients contain autoantibodies that react with tumor associated antigens (TAAs) that reflect genetic over-expression, mutation, or other anomalies of cell cycle, growth, signaling, and metabolism pathways.

Methods: We performed immunoassays to detect autoantibodies to ten tumor associated antigens (TAAs) selected on the basis of previous studies showing that they had preferential specificity for certain cancers. Sera examined were from lung cancer patients (22); smokers with ground-glass opacities (GGOs) (46), benign solid nodules (55), or normal CTs (35); and normal non-smokers (36). Logistic regression models based on the antibody biomarker levels among the high risk and lung cancer groups were developed to identify the combinations of biomarkers that predict lung cancer in these cohorts.

Results: Statistically significant differences in the distributions of each of the biomarkers were identified among all five groups. Using Receiver Operating Characteristic (ROC) curves based on age, c-myc, Cyclin A, Cyclin B1, Cyclin D1, CDK2, and survivin, we obtained a sensitivity = 81% and specificity = 97% for the classification of cancer vs smokers(no nodules, solid nodules, or GGO) and correctly predicted 31/36 healthy controls as noncancer.

Conclusion: A pattern of autoantibody reactivity to TAAs may distinguish patients with lung cancer versus smokers with normal CTs, stable solid nodules, ground glass opacities, or normal healthy never smokers.

Figures

Figure 1
Figure 1
Box plots of Age and Autoantibodies to TAAs by Classification Group. TAAs: p53, c-myc, IMP1, P62/IMP2, IMP3/KOC, Cyclin A, Cyclin B1, Cyclin D1, CDK2, Survivin. Classification Group: con-control, non-no nodule, sn-solid nodule, ggo-ground glass opacities, canc-cancer.
Figure 2
Figure 2
ROC Curve Based on Stepwise Multiple Logistic Regression and Log Transformed Biomarkers to Classify Cancer/No Cancer (no nodules, solid nodules, and ground glass opacities groups).

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