Section of Computational Biomedicine, Department of Medicine and BU-BMC Cancer Center, Boston University, Boston, Massachusetts.
Clin Cancer Res. 2018 Jul 1;24(13):2984-2992. doi: 10.1158/1078-0432.CCR-16-3187. Epub 2018 Feb 20.
Lung cancer remains the leading cause of cancer-related death due to its advanced stage at diagnosis. Early detection of lung cancer can be improved by better defining who should be screened radiographically and determining which imaging-detected pulmonary nodules are malignant. Gene expression biomarkers measured in normal-appearing airway epithelium provide an opportunity to use lung cancer-associated molecular changes in this tissue for early detection of lung cancer. Molecular changes in the airway may result from an etiologic field of injury and/or field cancerization. The etiologic field of injury reflects the aberrant physiologic response to carcinogen exposure that creates a susceptible microenvironment for cancer initiation. In contrast, field cancerization reflects effects of "first-hit" mutations in a clone of cells from which the tumor ultimately arises or the effects of the tumor on the surrounding tissue. These fields might have value both for assessing lung cancer risk and diagnosis. Cancer-associated gene expression changes in the bronchial airway have recently been used to develop and validate a 23-gene classifier that improves the diagnostic yield of bronchoscopy for lung cancer among intermediate-risk patients. Recent studies have demonstrated that these lung cancer-related gene expression changes extend to nasal epithelial cells that can be sampled noninvasively. While the bronchial gene expression biomarker is being adopted clinically, further work is necessary to explore the potential clinical utility of gene expression profiling in the nasal epithelium for lung cancer diagnosis, lung cancer risk assessment, and precision medicine for lung cancer treatment and chemoprevention. .
由于肺癌在诊断时已处于晚期，因此仍是导致癌症相关死亡的主要原因。通过更好地确定应进行影像学筛查的人群以及确定哪些影像学检测到的肺结节为恶性，可以提高肺癌的早期发现。在正常气道上皮中测量的基因表达生物标志物为利用该组织中与肺癌相关的分子变化进行肺癌的早期检测提供了机会。气道中的分子变化可能是由于损伤的病因学领域和/或肿瘤发生的领域所致。病因学领域反映了对致癌物暴露的异常生理反应，为癌症发生创造了易感的微环境。相比之下，肿瘤发生领域反映了肿瘤最终起源的细胞克隆中的“首次打击”突变的影响，或肿瘤对周围组织的影响。这些领域对于评估肺癌风险和诊断都可能具有价值。支气管气道中的癌症相关基因表达变化最近已被用于开发和验证 23 个基因分类器，该分类器可提高中危患者支气管镜检查对肺癌的诊断收益。最近的研究表明，这些与肺癌相关的基因表达变化扩展到了可以无创采样的鼻腔上皮细胞。虽然支气管基因表达生物标志物正在被临床采用，但仍需要进一步研究，以探索鼻上皮基因表达谱在肺癌诊断、肺癌风险评估以及肺癌治疗和化学预防的精准医学中的潜在临床应用。
