A major challenge in lung cancer prevention and cure hinges on identifying the at-risk population that 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. The purpose of this study is to validate, in an independent cohort, a selected list of 55 candidate proteins associated with risk for lung cancer with sensitive targeted proteomics using selected reaction monitoring (SRM). Bronchial brushings collected from individuals at low and high risk for developing lung cancer as well as patients with lung cancer, from both a subset of the original cohort (batch 1: n = 10 per group) and an independent cohort of 149 individuals (batch 2: low risk (n = 32), high risk (n = 34), and lung cancer (n = 83)), were analyzed using multiplexed SRM assays. ALDH3A1 and AKR1B10 were found to be consistently overexpressed in the high-risk group in both batch 1 and batch 2 brushing specimens as well as in the biopsies of batch 1. Validation of highly discriminatory proteins and metabolic enzymes by SRM in a larger independent cohort supported their use to identify patients at high risk for developing lung cancer.
肺癌预防与治疗的一个主要挑战在于识别最终会发展为肺癌的高危人群。先前,我们报道了从肺癌高危个体支气管刷检中获取的细胞学正常支气管上皮细胞的蛋白质组学改变。本研究旨在通过使用选择反应监测(SRM)的灵敏靶向蛋白质组学技术,在一个独立队列中对筛选出的55种与肺癌风险相关的候选蛋白进行验证。研究分析了来自肺癌低危和高危个体以及肺癌患者的支气管刷检样本,这些样本既包括原始队列的子集(批次1:每组n=10),也包括一个包含149名个体的独立队列(批次2:低危组n=32,高危组n=34,肺癌组n=83),并采用了多重SRM检测方法。结果发现,在批次1和批次2的刷检样本以及批次1的活检组织中,ALDH3A1和AKR1B10在高危组中均持续过表达。通过SRM在更大的独立队列中对高鉴别性蛋白及代谢酶进行验证,支持了这些生物标志物在识别肺癌高危患者中的应用价值。