The Airway Transcriptome as a Biomarker for Early Lung Cancer Detection.
The Airway Transcriptome as a Biomarker for Early Lung Cancer Detection.
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DOI：
10.1158/1078-0432.ccr-16-3187
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发表时间：
2018-07-01
期刊：
影响因子：
--
通讯作者：
Spira AE
中科院分区：
文献类型：
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作者：
Billatos E;Vick JL;Lenburg ME;Spira AE
肺癌仍然是癌症相关死亡的主要原因，因为其诊断时处于晚期。通过更好地确定哪些人应该接受放射学筛查，并确定哪些影像学检测到的肺结节是恶性的，可以改善肺癌的早期检测。在正常的气道上皮细胞中测量的基因表达生物标志物提供了利用该组织中肺癌相关分子变化进行肺癌早期检测的机会。呼吸道的分子变化可能是由损伤和/或癌变的病因引起的。损伤的病因学领域反映了对致癌物暴露的异常生理反应，其产生了癌症起始的易感微环境。相反，实地癌变反映了肿瘤最终产生的细胞克隆中的"首发"突变的影响或肿瘤对周围组织的影响。这些领域可能对评估肺癌风险和诊断都有价值。支气管气道中的癌症相关基因表达变化最近被用于开发和验证23基因分类器，该分类器提高了支气管镜检查对中危患者肺癌的诊断率。最近的研究表明，这些肺癌相关的基因表达变化延伸到鼻上皮细胞，可以非侵入性采样。虽然支气管基因表达生物标志物正在临床上被采用，但有必要进一步研究鼻上皮基因表达谱在肺癌诊断、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。
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 physiological 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 non-invasively. 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, risk assessment, and precision medicine for lung cancer treatment and chemoprevention.