Yan Xinmin, Yang Mingxia, Liu Juan, Gao Ruichen, Hu Jihong, Li Jiong, Zhang Lijun, Shi Yujia, Guo Hongrong, Cheng Jinluo, Razi Miriam, Pang Shen, Yu Xiaowei, Hu Shen
Changzhou Second People's Hospital, Nanjing Medical University Changzhou, 213003, China.
School of Dentistry and Jonsson Comprehensive Cancer Center, University of California Los Angeles, CA 90095, USA.
Am J Cancer Res. 2015 Sep 15;5(10):3111-22. eCollection 2015.
Microbes are residents in a number of body sites, including the oral and nasal cavities, which are connected to the lung via the pharynx. The associations between oral diseases and increased risk of lung cancer have been reported in previous prospective studies. In this study, we measured variations of salivary microbiota and evaluated their potential association with lung cancer, including squamous cell carcinoma (SCC) and adenocarcinoma (AC). A three-phase study was performed: First, we investigated the salivary microbiota from 20 lung cancer patients (10 SCC and 10 AC) and control subjects (n=10) using a deep sequencing analysis. Salivary Capnocytophaga, Selenomonas, Veillonella and Neisseria were found to be significantly altered in patients with SCC and AC when compared to that in control subjects. Second, we confirmed the significant changes of Capnocytophaga, Veillonella and Neisseria in the same lung cancer patients using quantitative PCR (qPCR). Finally, these bacterial species were further validated on new patient/control cohorts (n=56) with qPCR. The combination of two bacterial biomarkers, Capnocytophaga and Veillonella, yielded a receiver operating characteristic (ROC) value of 0.86 with an 84.6% sensitivity and 86.7% specificity in distinguishing patients with SCC from control subjects and a ROC value of 0.80 with a 78.6% sensitivity and 80.0% specificity in distinguishing patients with AC from control subjects. In conclusion, we have for the first time demonstrated the association of saliva microbiota with lung cancer. Particularly, the combination of the 16S sequencing discovery with qPCR validation studies revealed that the levels of Capnocytophaga and Veillonella were significantly higher in the saliva from lung cancer patients, which may serve as potential biomarkers for the disease detection/classification.
微生物是许多身体部位的常驻菌群,包括口腔和鼻腔,它们通过咽部与肺部相连。先前的前瞻性研究已经报道了口腔疾病与肺癌风险增加之间的关联。在本研究中,我们测量了唾液微生物群的变化,并评估了它们与肺癌(包括鳞状细胞癌(SCC)和腺癌(AC))的潜在关联。我们进行了一项分三个阶段的研究:首先,我们使用深度测序分析调查了20名肺癌患者(10名SCC患者和10名AC患者)和对照组(n = 10)的唾液微生物群。与对照组相比,SCC和AC患者的唾液二氧化碳嗜纤维菌、纤细螺旋体菌、韦荣氏菌属和奈瑟氏菌属有显著变化。其次,我们使用定量PCR(qPCR)在同一批肺癌患者中证实了二氧化碳嗜纤维菌、韦荣氏菌属和奈瑟氏菌属的显著变化。最后,使用qPCR在新的患者/对照队列(n = 56)中进一步验证了这些细菌种类。两种细菌生物标志物——二氧化碳嗜纤维菌和韦荣氏菌属的组合,在区分SCC患者与对照组时,受试者工作特征(ROC)值为0.86,灵敏度为84.6%,特异性为86.7%;在区分AC患者与对照组时,ROC值为0.80,灵敏度为78.6%,特异性为80.0%。总之,我们首次证明了唾液微生物群与肺癌之间的关联。特别是,16S测序发现与qPCR验证研究相结合表明,肺癌患者唾液中二氧化碳嗜纤维菌和韦荣氏菌属的水平显著更高,这可能作为该疾病检测/分类的潜在生物标志物。