J Natl Cancer Inst. 2017 Jul 1;109(7). doi: 10.1093/jnci/djw327.
We previously derived and validated a bronchial epithelial gene expression biomarker to detect lung cancer in current and former smokers. Given that bronchial and nasal epithelial gene expression are similarly altered by cigarette smoke exposure, we sought to determine if cancer-associated gene expression might also be detectable in the more readily accessible nasal epithelium.
Nasal epithelial brushings were prospectively collected from current and former smokers undergoing diagnostic evaluation for pulmonary lesions suspicious for lung cancer in the AEGIS-1 (n = 375) and AEGIS-2 (n = 130) clinical trials and gene expression profiled using microarrays. All statistical tests were two-sided.
We identified 535 genes that were differentially expressed in the nasal epithelium of AEGIS-1 patients diagnosed with lung cancer vs those with benign disease after one year of follow-up ( P < .001). Using bronchial gene expression data from the AEGIS-1 patients, we found statistically significant concordant cancer-associated gene expression alterations between the two airway sites ( P < .001). Differentially expressed genes in the nose were enriched for genes associated with the regulation of apoptosis and immune system signaling. A nasal lung cancer classifier derived in the AEGIS-1 cohort that combined clinical factors (age, smoking status, time since quit, mass size) and nasal gene expression (30 genes) had statistically significantly higher area under the curve (0.81; 95% confidence interval [CI] = 0.74 to 0.89, P = .01) and sensitivity (0.91; 95% CI = 0.81 to 0.97, P = .03) than a clinical-factor only model in independent samples from the AEGIS-2 cohort.
These results support that the airway epithelial field of lung cancer-associated injury in ever smokers extends to the nose and demonstrates the potential of using nasal gene expression as a noninvasive biomarker for lung cancer detection.
我们之前推导并验证了一种支气管上皮基因表达生物标志物，用于在现吸烟者和既往吸烟者中检测肺癌。鉴于香烟烟雾暴露对支气管和鼻上皮基因表达的改变相似，我们试图确定在更容易获取的鼻上皮中是否也能检测到与癌症相关的基因表达。
在AEGIS - 1（n = 375）和AEGIS - 2（n = 130）临床试验中，前瞻性收集了接受肺部病变诊断评估的现吸烟者和既往吸烟者的鼻上皮刷片，这些病变疑似肺癌，并使用微阵列对基因表达进行分析。所有统计检验均为双侧检验。
我们鉴定出535个基因，在随访一年后，被诊断为肺癌的AEGIS - 1患者的鼻上皮与患有良性疾病的患者相比，这些基因存在差异表达（P <.001）。利用AEGIS - 1患者的支气管基因表达数据，我们发现两个气道部位之间存在具有统计学意义的一致的癌症相关基因表达改变（P <.001）。鼻中差异表达的基因富含与细胞凋亡调节和免疫系统信号传导相关的基因。在AEGIS - 1队列中得出的一种鼻肺癌分类器，结合了临床因素（年龄、吸烟状态、戒烟时间、肿块大小）和鼻基因表达（30个基因），在来自AEGIS - 2队列的独立样本中，其曲线下面积（0.81；95%置信区间[CI] = 0.74至0.89，P =.01）和敏感性（0.91；95% CI = 0.81至0.97，P =.03）在统计学上显著高于仅包含临床因素的模型。
这些结果支持，既往吸烟者中与肺癌相关损伤的气道上皮区域延伸至鼻子，并证明了使用鼻基因表达作为肺癌检测的非侵入性生物标志物的潜力。
