期刊
JOURNAL OF PROTEOME RESEARCH
卷 16, 期 9, 页码 3266-3276出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.7b00245
关键词
lung cancer; granuloma; parallel reaction monitoring; adenocarcinoma; indeterminate pulmonary nodule
资金
- NCI/NIH Cancer Center Support Grant [2P30 CA068485-14]
- Vanderbilt Mouse Metabolic Phenotyping Center [5U24DK059637-13]
- National Institutes of Health [R01CA102353, U01CA152662]
- National Institutes of Health (Lung SPORE) [P50CA90949, U01CA152647]
- Department of Defense [W81XWH-11-2-0161, CDMRP LC090615P3]
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 ALOXS, ALOXSAP, CCL19, CILP1, COL5A2, ITGB2, ITGAX, PTPRE, S100Al2, 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 ALOXS, ALOXSAP, 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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