Blood-based lung cancer biomarkers identified through proteomic discovery in cancer tissues, cell lines and conditioned medium.

ABSTRACT: BACKGROUND:Support for early detection of lung cancer has emerged from the National Lung Screening Trial (NLST), in which low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20 % relative to chest x-ray. The US Preventive Services Task Force (USPSTF) recently recommended annual screening for the high-risk population, concluding that the benefits (life years gained) outweighed harms (false positive findings, abortive biopsy/surgery, radiation exposure). In making their recommendation, the USPSTF noted that the moderate net benefit of screening was dependent on the resolution of most false-positive results without invasive procedures. Circulating biomarkers may serve as a valuable adjunctive tool to imaging. RESULTS:We developed a broad-based proteomics discovery program, integrating liquid chromatography/mass spectrometry (LC/MS) analyses of freshly resected lung tumor specimens (n?=?13), lung cancer cell lines (n?=?17), and conditioned media collected from tumor cell lines (n?=?7). To enrich for biomarkers likely to be found at elevated levels in the peripheral circulation of lung cancer patients, proteins were prioritized based on predicted subcellular localization (secreted, cell-membrane associated) and differential expression in disease samples. 179 candidate biomarkers were identified. Several markers selected for further validation showed elevated levels in serum collected from subjects with stage I NSCLC (n?=?94), relative to healthy smoker controls (n?=?189). An 8-marker model was developed (TFPI, MDK, OPN, MMP2, TIMP1, CEA, CYFRA 21-1, SCC) which accurately distinguished subjects with lung cancer (n?=?50) from high risk smokers (n?=?50) in an independent validation study (AUC?=?0.775). CONCLUSIONS:Integrating biomarker discovery from multiple sample types (fresh tissue, cell lines and conditioned medium) has resulted in a diverse repertoire of candidate biomarkers. This unique collection of biomarkers may have clinical utility in lung cancer detection and diagnoses.

SUBMITTER: Birse CE 

PROVIDER: S-EPMC4537594 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature