Objective:We aimed to prospectively evaluate the association of oral microbiome with malignant esophageal lesions and its predictive potential as a biomarker of risk.Methods:We conducted a case-control study nested wi...Objective:We aimed to prospectively evaluate the association of oral microbiome with malignant esophageal lesions and its predictive potential as a biomarker of risk.Methods: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 16 S 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.Results: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 screenendoscopic-detected or clinically diagnosed case-control triads,or using only bacterial data measured at the baseline,yielded AUCs>0.84.Conclusions: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.展开更多
Objective： This study aimed to comprehensively assess Epstein-Barr virus（EBV）-induced methylation alterations of B cell across whole genome.Methods： We compared DNA methylation patterns of primary B cells and corr...Objective： This study aimed to comprehensively assess Epstein-Barr virus（EBV）-induced methylation alterations of B cell across whole genome.Methods： We compared DNA methylation patterns of primary B cells and corresponding lymphoblastoid cell lines（LCLs） from eight participants. The genome-wide DNA methylation profiles were compared at over 850,000 genome-wide methylation sites.Results： DNA methylation analysis revealed 87,732 differentially methylated Cp G sites, representing approximately 12.41% of all sites in LCLs compared to primary B cells. The hypermethylated and hypomethylated Cp G sites were about 22.75% or 77.25%, respectively. Only 0.8% of hypomethylated sites and 4.5% of hypermethylated sites were located in Cp G islands, whereas 8.0% of hypomethylated sites and 16.3% of hypermethylated sites were located in shore（N_shore and S_shore）. Using principal component analysis of the DNA methylation profiles, primary B cells and LCLs could be accurately predicted. Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） analysis of differently methylated genes revealed that most of the top GO biological processes were related to cell activation and immune response, and some top enrichment pathways were related with activation and malignant transformation of human B cells.Conclusions： Our study demonstrated genome-wide DNA methylation variations between primary B cells and corresponding LCLs, which might yield new insight on the methylation mechanism of EBV-induced immortalization.展开更多
基金the National Natural Science Foundation of China(No.30930102,82073626,81502855,81773501)the National Key R&D program of China(No.2016YFC0901404)+4 种基金the National Special Programme of Scientific and Technological Resources Investigation(No.2019FY101102)the Digestive Medical Coordinated Development Center of Beijing Hospitals Authority(No.XXZ0204)the Beijing Natural Science Foundation(No.7182033)the Beijing Municipal Administration of Hospital’s Youth Programme(No.QML20171101)the Science Foundation of Peking University Cancer Hospital(No.2020-7)。
文摘Objective:We aimed to prospectively evaluate the association of oral microbiome with malignant esophageal lesions and its predictive potential as a biomarker of risk.Methods: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 16 S 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.Results: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 screenendoscopic-detected or clinically diagnosed case-control triads,or using only bacterial data measured at the baseline,yielded AUCs>0.84.Conclusions: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.
基金supported by grants from National Natural Science Foundation of China (No. 81160249, 81301886 and 81760525)Science Foundation of Peking University Cancer Hospital (No. 2017 Zizhu-1)+4 种基金Open Project funded by Key Laboratory of Carcinogenesis and Translational ResearchMinistry of Education/Beijing (2017 Open Project-3)Beijing Municipal Science & Technology Commission (No. Z171100001017136)Beijing Natural Science Foundation (No. 7171001)West China First-Class Discipline Construction Project in Basic Medicine funded by Ningxia Medical University
文摘Objective： This study aimed to comprehensively assess Epstein-Barr virus（EBV）-induced methylation alterations of B cell across whole genome.Methods： We compared DNA methylation patterns of primary B cells and corresponding lymphoblastoid cell lines（LCLs） from eight participants. The genome-wide DNA methylation profiles were compared at over 850,000 genome-wide methylation sites.Results： DNA methylation analysis revealed 87,732 differentially methylated Cp G sites, representing approximately 12.41% of all sites in LCLs compared to primary B cells. The hypermethylated and hypomethylated Cp G sites were about 22.75% or 77.25%, respectively. Only 0.8% of hypomethylated sites and 4.5% of hypermethylated sites were located in Cp G islands, whereas 8.0% of hypomethylated sites and 16.3% of hypermethylated sites were located in shore（N_shore and S_shore）. Using principal component analysis of the DNA methylation profiles, primary B cells and LCLs could be accurately predicted. Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） analysis of differently methylated genes revealed that most of the top GO biological processes were related to cell activation and immune response, and some top enrichment pathways were related with activation and malignant transformation of human B cells.Conclusions： Our study demonstrated genome-wide DNA methylation variations between primary B cells and corresponding LCLs, which might yield new insight on the methylation mechanism of EBV-induced immortalization.
