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

Clinical Proteomics

Gulshan Dhariwal³  Jenny Heidbrink³  Aaron O. Bungum⁴  Aiqun Li³  Charles E. Birse³  Steve M. Ruben³  Elizabeth Joseloff³  Jennifer L. Tomic³  Paul A. Moore³  Chad Danis³  Harvey I. Pass¹  Robert J. Bruce³  James R. Jett⁵  Marcia E. Lewis³  William FitzHugh³  Mehdi Mesri³  Tao He³  Fabien Maldonado⁴  William N. Rom²  Erin Sult³  Eric S. Edell⁴  Robert J. Lagier³ 

[1] Department of Cardiothoracic Surgery, NYU Langone Medical Center, New York, USADepartment of Cardiothoracic Surgery, NYU Langone Medical Center, New York, USADepartment of Cardiothoracic Surgery, NYU Langone Medical Center, New York, USA;Division of Pulmonary, Critical Care, and Sleep Medicine, NYU School of Medicine, New York, USADivision of Pulmonary, Critical Care, and Sleep Medicine, NYU School of Medicine, New York, USADivision of Pulmonary, Critical Care, and Sleep Medicine, NYU School of Medicine, New York, USA;Celera employees during the course of these studies, Alameda, USACelera employees during the course of these studies, Alameda, USACelera employees during the course of these studies, Alameda, USA;Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, USADivision of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, USADivision of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, USA;Division of Oncology, National Jewish Health, Denver, USADivision of Oncology, National Jewish Health, Denver, USADivision of Oncology, National Jewish Health, Denver, USA

关键词: Lung cancer;    Early detection;    Biomarker;    Mass spectrometry;    Proteomics;    Discovery;   

DOI  :  10.1186/s12014-015-9090-9

来源: Humana Press Inc

【 摘 要 】

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.

【 授权许可】

Unknown