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Publication
Identification of Proteomic Features To Distinguish Benign Pulmonary Nodules
from Lung Adenocarcinoma.
Authors Codreanu SG, Hoeksema MD, Slebos RJC, Zimmerman LJ, Rahman SMJ, Li M, Chen SC,
Chen H, Eisenberg R, Liebler DC, Massion PP
Submitted By Submitted Externally on 1/25/2019
Status Published
Journal Journal of proteome research
Year 2017
Date Published 9/1/2017
Volume : Pages 16 : 3266 - 3276
PubMed Reference 28731711
Abstract We hypothesized that distinct protein expression features of benign and
malignant pulmonary nodules may reveal novel candidate biomarkers for the early
detection of lung cancer. We performed proteome profiling by liquid
chromatography-tandem mass spectrometry to characterize 34 resected benign lung
nodules, 24 untreated lung adenocarcinomas (ADCs), and biopsies of bronchial
epithelium. Group comparisons identified 65 proteins that differentiate nodules
from ADCs and normal bronchial epithelium and 66 proteins that differentiate
ADCs from nodules and normal bronchial epithelium. We developed a multiplexed
parallel reaction monitoring (PRM) assay to quantify a subset of 43 of these
candidate biomarkers in an independent cohort of 20 benign nodules, 21 ADCs, and
20 normal bronchial biopsies. PRM analyses confirmed significant nodule-specific
abundance of 10 proteins including ALOX5, ALOX5AP, CCL19, CILP1, COL5A2, ITGB2,
ITGAX, PTPRE, S100A12, and SLC2A3 and significant ADC-specific abundance of
CEACAM6, CRABP2, LAD1, PLOD2, and TMEM110-MUSTN1. Immunohistochemistry analyses
for seven selected proteins performed on an independent set of tissue
microarrays confirmed nodule-specific expression of ALOX5, ALOX5AP, ITGAX, and
SLC2A3 and cancer-specific expression of CEACAM6. These studies illustrate the
value of global and targeted proteomics in a systematic process to identify and
qualify candidate biomarkers for noninvasive molecular diagnosis of lung cancer.




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