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J Proteome Res. 2017 Sep 1;16(9):3266-3276. doi: 10.1021/acs.jproteome.7b00245. Epub 2017 Aug 8.

Identification of Proteomic Features To Distinguish Benign Pulmonary Nodules from Lung Adenocarcinoma.

Author information

1
Department of Biochemistry, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
2
Department of Biostatistics, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
3
Center for Quantitative Sciences, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
4
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
5
Department of Cancer Biology, Vanderbilt University Medical Center , Nashville, Tennessee 37232, United States.
6
Veterans Affairs, Tennessee Valley Healthcare System , Nashville, Tennessee 37212, United States.

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.

KEYWORDS:

adenocarcinoma; granuloma; indeterminate pulmonary nodule; lung cancer; parallel reaction monitoring

PMID:
28731711
PMCID:
PMC6339813
DOI:
10.1021/acs.jproteome.7b00245
[Indexed for MEDLINE]
Free PMC Article

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