Liu Fangfang, Liu Mengfei, Liu Ying, Guo Chuanhai, Zhou Yunlai, Li Fenglei, Xu Ruiping, Liu Zhen, Deng Qiuju, Li Xiang, Zhang Chaoting, Pan Yaqi, Ning Tao, Dong Xiao, Hu Zhe, Bao Huanyu, Cai Hong, Silva Isabel Dos Santos, He Zhonghu, Ke Yang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Novogene Co., Ltd, Beijing 100080, China.
Chin J Cancer Res. 2020 Dec 31;32(6):742-754. doi: 10.21147/j.issn.1000-9604.2020.06.07.
We aimed to prospectively evaluate the association of oral microbiome with malignant esophageal lesions and its predictive potential as a biomarker of risk.
We conducted a case-control study nested within a population-based cohort with up to 8 visits of oral swab collection for each subject over an 11-year period in a high-risk area for esophageal cancer in China. The oral microbiome was evaluated with 16S ribosomal RNA (rRNA) gene sequencing in 428 pre-diagnostic oral specimens from 84 cases with esophageal lesions of severe squamous dysplasia and above (SDA) and 168 matched healthy controls. DESeq analysis was performed to identify taxa of differential abundance. Differential oral species together with subject characteristics were evaluated for their potential in predicting SDA risk by constructing conditional logistic regression models.
A total of 125 taxa including 37 named species showed significantly different abundance between SDA cases and controls (all P<0.05 & false discovery rate-adjusted Q<0.10). A multivariate logistic model including 11 SDA lesion-related species and family history of esophageal cancer provided an area under the receiver operating characteristic curve (AUC) of 0.89 (95% CI, 0.84-0.93). Cross-validation and sensitivity analysis, excluding cases diagnosed within 1 year of collection of the baseline specimen and their matched controls, or restriction to screen-endoscopic-detected or clinically diagnosed case-control triads, or using only bacterial data measured at the baseline, yielded AUCs>0.84.
The oral microbiome may play an etiological and predictive role in esophageal cancer, and it holds promise as a non-invasive early warning biomarker for risk stratification for esophageal cancer screening programs.
我们旨在前瞻性评估口腔微生物群与食管恶性病变的关联及其作为风险生物标志物的预测潜力。
我们在中国食管癌高发地区开展了一项病例对照研究，该研究嵌套于一项基于人群的队列研究中，每位受试者在11年期间接受多达8次口腔拭子采集。通过对84例重度鳞状上皮发育异常及以上（SDA）食管病变患者和168例匹配的健康对照的428份诊断前口腔标本进行16S核糖体RNA（rRNA）基因测序来评估口腔微生物群。进行DESeq分析以识别丰度有差异的分类群。通过构建条件逻辑回归模型，评估差异口腔物种以及受试者特征预测SDA风险的潜力。
共有125个分类群（包括37个已命名物种）在SDA病例和对照之间表现出显著不同的丰度（所有P<0.0５且错误发现率调整后的Q<0.10）。一个包含11种与SDA病变相关的物种和食管癌家族史的多变量逻辑模型的受试者操作特征曲线下面积（AUC）为0.89（95%CI，0.84-0.93）。交叉验证和敏感性分析，排除在基线标本采集后1年内诊断的病例及其匹配对照，或限制为筛查内镜检测或临床诊断的病例对照三联体，或仅使用基线时测量的细菌数据，得到的AUC>0.84。
口腔微生物群可能在食管癌中发挥病因学和预测作用，有望作为一种非侵入性早期预警生物标志物用于食管癌筛查项目的风险分层。
