Qualification and verification of serological biomarker candidates for lung adenocarcinoma by targeted mass spectrometry

Abstract

Lung cancer is the leading cause of cancer mortality worldwide The main reasons of the high mortality of lung cancer are absence of the useful tools to diagnose lung cancer at early stage and lack of effective treatments for metastatic cancer To find biomarkers that are sensitive and specific to the early-stage lung cancer become an important issue which provides huge benefit for lung cancer prevention Nowadays there is plenty of biomarker discovery-based research finished many proteins have been reported that they were associated with the cancer progression and have the opportunities to sever as cancer markers However for the application concern the diagnosis/prognosis performances of the protein candidates need to be validated in the blood The recent emergence of targeted mass spectrometry based proteomic technology (MRM) analysis is able to test tens or even hundreds of protein candidates in one LC-MS/MS run and already became a principal enabling method for biomarker validation In this study we attempted to conduct a MRM-based targeted analysis to evaluate the potential utility of a list of protein candidates for lung cancer diagnosis in the blood samples A total of 1249 transitions of 420 peptides representing 102 protein candidates from our previous study and literature were first screened by MRM analysis in the polled plasma samples remaining 78 proteins in the list Relative quantification of these 78 proteins was further performed in individual plasma sample from patients in 3 stages and 30 paired healthy donors Ultimately 9 proteins were found to be able to distinguished patients from controls Further combination of 5 3 and 2 candidate marker proteins has improved sensitivity in discrepancy power as well as a merged AUC value of nearly 1 00 in stage I II III groups versus controls respectively Our result has highlighted several possible markers for lung adenocarcinoma and the proposed protein panels append further validation in a larger cohort for evaluating their potential use in clinical applications or development of therapeutics

Date of Award	2014 Aug 27
Original language	English
Supervisor	Pao-Chi Liao (Supervisor)