Abstract 1620: Validation of a proteomic signature of lung cancer risk from bronchial brushings
Authors: SM Jamshedur Rahman, Yuqian Gao, Athena A. Schepmoes, Yi-Ting Wang, Tujin Shi, Sheau-Chiann Chen, Heidi Chen, Karin D. Rodland, Tao Liu, Pierre P. Massion
Journal: Cancer Research (2019)

Abstract A major challenge in lung cancer prevention and cure hinges on identifying the at-risk population who ultimately develops lung cancer. Previously we reported proteomic alterations in the cytologically normal bronchial epithelial cells collected from the bronchial brushings of individuals at-risk for lung cancer. Proteins were identified by shotgun proteomics using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and selected candidate biomarkers of risk were validated in an independent sample cohort by parallel reaction monitoring. The purpose of the current study is to validate, in independent cohorts from Vanderbilt University Medical Center, a selected list of 54 candidate proteins associated with risk for lung cancer with sensitive targeted proteomics using selected reaction monitoring (SRM) at the Pacific Northwest National Laboratory. We tested proteins from bronchial brushings and bronchial biopsies collected from individuals at low risk (n=10) and high risk (n=10) based on the Tammemagi risk stratification model as well as from patients with lung cancer (n=10). Multiplexed LC-SRM assays were developed for all 54 proteins and the protein concentrations were determined by LC-SRM using heavy isotope-labeled peptides for 44 and 49 proteins in the brushings and biopsy samples, respectively. Pairwise comparisons by Wilcoxon rank sum test demonstrated significant overexpression, in the high-risk group compared to the low-risk group, of ALDH3A1 and AKR1B10 in both brushings and biopsies, and of SFN/YWHAS only in the biopsies. Significant overexpression of ALDH1A1, ALDH3A1, AKR1B10, ANXA1, CTNNB1, G6PD, LGALS7B, ALOX15, PGK1, SFN/YWHAS, and UBA1 were observed in the lung cancer group compared to the low-risk group in the brushings only. LGALS7B was also overexpressed in the brushings of high risk compared to lung cancer group. In conclusion, these SRM results revealed promise of selected candidate proteins to stratify the at-risk population for lung cancer. Next, our validation efforts will test the promising candidates in second, larger independent cohort; methods with increased sensitivity such as PRISM (high-pressure, high-resolution separations with intelligent selection and multiplexing)-SRM for analysis of the previously undetected low abundant protein candidates and carrier-assisted SRM approaches for analysis of very small-sized samples. Ultimately, we hope to deliver a signature of risk that may provide the basis for lung cancer risk assessment and possibly novel future prevention strategies. This work is supported by UO1CA152662. Citation Format: SM Jamshedur Rahman, Yuqian Gao, Athena A. Schepmoes, Yi-Ting Wang, Tujin Shi, Sheau-Chiann Chen, Heidi Chen, Karin D. Rodland, Tao Liu, Pierre P. Massion. Validation of a proteomic signature of lung cancer risk from bronchial brushings [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1620.