Verification of serological lung adenocarcinoma protein markers using liquid chromatography multiple reaction monitoring mass spectrometry

Abstract

Lung cancer is the second most common cancer and the leading cause of cancer death in America Among all diagnosed lung cancer lung adenocarcinoma is the most common one Although several lung cancer markers have been studied no markers suitable for early detection have been validated which leads to an urgent need to discover more lung cancer-specific biomarkers for early detection A total of 35 stable isotope-labeled peptides are synthesized based on the previous study and are used as internal standards in liquid chromatography multiple reaction monitoring mass spectrometry (LC-MRM-MS) analysis Overall the specific aims of this study are (1) to compare the potential biomarkers between lung adenocarcinoma patients and healthy control in plasma using LC-MRM-MS with stable isotope-labeled peptides (2) To verify the biomarkers associated with early development of lung cancer using Mann-Whitney U test and receiver operating characteristic (ROC) curve (3) To discover other potentials of these biomarker candidates using survival analysis An LC-MRM-MS assay was used for measuring the level of 35 candidate peptides in plasma from 102 lung adenocarcinoma patients and 84 healthy controls Seven proteins were found to be able to distinguish stage I patients from controls These proteins were combined into a protein marker panel which improved the sensitivity to discriminate stage I patients from controls and resulted in a high classification performance with cross-validated area under the curve=0 76 Besides the low expression of eukaryotic initiation factor 4A-I and high expression of lumican showed significantly poor prognosis in overall survival (p=0 012 and 0 0074 respectively) which may be used as prognostic biomarkers for lung cancer The seven-protein panel may be used for early detection of lung adenocarcinoma or therapeutics development after validation in a larger cohort

Date of Award	2019
Original language	English
Supervisor	Pao-Chi Liao (Supervisor)