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.