Qualification and Verification of Serological Biomarker Candidates for Lung Adenocarcinoma by Targeted Mass Spectrometry

Lung cancer is the leading cause of cancer mortality worldwide. Although many biomarkers have been identified for lung cancer, their low specificity and sensitivity present an urgent need for the identification of more candidate biomarkers. In this study, we conducted MRM-based targeted analysis to evaluate the potential utility of a list of candidate proteins for lung cancer diagnosis. A total of 1249 transitions of 420 peptides representing 102 candidate proteins from our previous study and the literature were first screened by MRM analysis in pooled plasma samples, resulting in 78 proteins remaining in the list. Relative quantification of these 78 proteins was further performed in 60 individual plasma samples from lung adenocarcinoma patients in stages I-III and matched healthy control subjects. Ultimately, nine proteins were found to be able to distinguish patients from controls. Further combinations of five, three, and two candidate marker proteins improved the sensitivity to discriminate patients from controls and resulted in a merged AUC value of nearly 1.00 in stages I-III patients versus controls. Our results highlighted several possible markers for lung adenocarcinoma, and the proposed protein panels require further validation in a larger cohort to evaluate their potential use in clinical applications or development of therapeutics.