*Department of Research and Development, Proteomika SLU, Derio, Spain; and the †Department of Respiratory Medicine and ‡Medical Oncology Research Laboratory, Cruces Hospital, Barakaldo, Spain.
J Thorac Oncol. 2014 Oct;9(10):1504-12. doi: 10.1097/JTO.0000000000000282.
The enormous biological complexity and high mortality rate of lung cancer highlights the need for new global approaches for the discovery of reliable early diagnostic biomarkers. The study of bronchoalveolar lavage samples by proteomic techniques could identify new lung cancer biomarkers and may provide promising noninvasive diagnostic tools able to enhance the sensitivity of current methods.
First, an observational prospective study was designed to assess protein expression differences in bronchoalveolar lavages from patients with (n = 139) and without (n = 49) lung cancer, using two-dimensional gel electrophoresis and subsequent protein identification by mass spectrometry. Second, validation of candidate biomarkers was performed by bead-based immunoassays with a different patient cohort (204 patients, 48 controls).
Thirty-two differentially expressed proteins were identified in bronchoalveolar lavages, 10 of which were confirmed by immunoassays. The expression levels of APOA1, CO4A, CRP, GSTP1, and SAMP led to a lung cancer diagnostic panel that reached 95% sensitivity and 81% specificity, and the quantification of STMN1 and GSTP1 proteins allowed the two main lung cancer subtypes to be discriminated with 90% sensitivity and 57% specificity.
Bronchoalveolar lavage represents a promising noninvasive source of lung cancer specific protein biomarkers with high diagnostic accuracy. Measurement of APOA1, CO4A, CRP, GSTP1, SAMP, and STMN1 in this fluid may be a useful tool for lung cancer diagnosis, although a further validation in a larger clinical set is required for early stages.
肺癌的巨大生物学复杂性和高死亡率突出表明需要新的全球方法来发现可靠的早期诊断生物标志物。通过蛋白质组学技术研究支气管肺泡灌洗液可以识别新的肺癌生物标志物，并可能提供有前途的非侵入性诊断工具，能够提高当前方法的灵敏度。
首先，设计了一项观察性前瞻性研究，以使用二维凝胶电泳和随后的质谱法鉴定来自患有（n = 139）和不患有（n = 49）肺癌的患者的支气管肺泡灌洗液中的蛋白表达差异。其次，通过 bead-based immunoassays 对不同的患者队列（204 例患者，48 例对照）进行候选生物标志物的验证。
在支气管肺泡灌洗液中鉴定出 32 种差异表达的蛋白质，其中 10 种通过免疫测定得到证实。APOA1、CO4A、CRP、GSTP1 和 SAMP 的表达水平导致肺癌诊断小组达到 95%的灵敏度和 81%的特异性，并且 STMN1 和 GSTP1 蛋白的定量允许以 90%的灵敏度和 57%的特异性区分两种主要的肺癌亚型。
支气管肺泡灌洗液是一种很有前途的非侵入性肺癌特异性蛋白生物标志物来源，具有很高的诊断准确性。在这种液体中测量 APOA1、CO4A、CRP、GSTP1、SAMP 和 STMN1 可能是肺癌诊断的有用工具，尽管需要在更大的临床样本中进一步验证早期阶段。
