title: Discovery and validation of potential bacterial biomarkers for lung cancer.
abstract: 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.
authors.affiliation: Changzhou Second People's Hospital, Nanjing Medical University Changzhou, 213003, China.
authors.forename: Xinmin
authors.initials: X
authors.lastname: Yan
authors.affiliation: Changzhou Second People's Hospital, Nanjing Medical University Changzhou, 213003, China.
authors.forename: Mingxia
authors.initials: M
authors.lastname: Yang
authors.affiliation: Changzhou Second People's Hospital, Nanjing Medical University Changzhou, 213003, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Changzhou Second People's Hospital, Nanjing Medical University Changzhou, 213003, China.
authors.forename: Ruichen
authors.initials: R
authors.lastname: Gao
authors.affiliation: Changzhou Second People's Hospital, Nanjing Medical University Changzhou, 213003, China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Hu
authors.affiliation: School of Dentistry and Jonsson Comprehensive Cancer Center, University of California Los Angeles, CA 90095, USA.
authors.forename: Jiong
authors.initials: J
authors.lastname: Li
authors.affiliation: David Geffen School of Medicine, University of California Los Angeles, CA 90095, USA.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Changzhou Second People's Hospital, Nanjing Medical University Changzhou, 213003, China.
authors.forename: Yujia
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Changzhou Second People's Hospital, Nanjing Medical University Changzhou, 213003, China.
authors.forename: Hongrong
authors.initials: H
authors.lastname: Guo
authors.affiliation: Changzhou Second People's Hospital, Nanjing Medical University Changzhou, 213003, China.
authors.forename: Jinluo
authors.initials: J
authors.lastname: Cheng
authors.affiliation: School of Dentistry and Jonsson Comprehensive Cancer Center, University of California Los Angeles, CA 90095, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Razi
authors.affiliation: David Geffen School of Medicine, University of California Los Angeles, CA 90095, USA.
authors.forename: Shen
authors.initials: S
authors.lastname: Pang
authors.affiliation: Changzhou Second People's Hospital, Nanjing Medical University Changzhou, 213003, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Yu
authors.affiliation: School of Dentistry and Jonsson Comprehensive Cancer Center, University of California Los Angeles, CA 90095, USA.
authors.forename: Shen
authors.initials: S
authors.lastname: Hu
keywords: 16S rDNA sequencing; Capnocytophaga; Lung cancer; Veillonella; saliva microbiota