Serum Antibodies in Lung Cancer: A proteomics approach in the NELSON trial

Lung cancer is currently one of the most common types of cancer with the highest mortality rate (28%) in the world. Eighty to ninety percent of all lung cancer patients are due to smoking. Only 15% of these patients are diagnosed at an early stage and can be operated. Therefore, it is important to detect lung cancer at an early stage. Studies have proven that CT screening can detect lung cancer at an early stage. Unfortunately, about 27% of the patients are incorrectly diagnosed for lung cancer which gives unnecessary stress to the patient and/or unnecessary surgeries. Biomarkers may be useful complementary to CT screening. Research has been performed on finding a biomarker for lung cancer, but despite the good sensitivity and specificity, these biomarkers are not validated or they were not reproducible. This thesis shows a different approach than those used by other studies. Tumors are thought to induce the release of many TAAs (tumor-associated antigens) into the blood, resulting in production of auto-antibodies against these antigens. In this thesis, we show a method that can be used for finding a biomarker for (lung) cancer or autoimmune diseases. The method which has been developed is based on sequencing and quantification of IgG Fab and CDRs (complementarity determining regions) using mass spectrometry and showed that identification of Fab fragments for use as a biomarker can be realized. This method we applied to lung cancer patients and controls from the NELSON trial. We found an antibody-peptide model that could distinguish lung cancer patients from controls with a sensitivity of 96% and specificity of 100%. This model has been validated with a sensitivity of 84% and a specificity of 90%. The results indicate that specific antibodies are able to detect lung cancer at an earlier stage than CT screening since the samples that have been used were obtained at an early stage. Auto-antibody profiling has the potential to be a powerful additional test for early detection of lung cancer in a screening strategy. More research is required to assess the use of these peptides in a clinical setting.

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