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A Preliminary Study On The Relationship Between Oral Microbial Ecology And Oral Squamous Cell Carcinoma

Posted on:2019-06-10Degree:DoctorType:Dissertation
Country:ChinaCandidate:H S ZhaoFull Text:PDF
GTID:1484305894458064Subject:Oral and clinical medicine
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Objectives:Oral squamous cell carcinoma(OSCC)is a common malignant tumor of head and neck,with low 5-year survival rate,and high risk of recurrence,being a serious threat of public health.Microorganism has been reported to be involved in different carcinomas,but the association between oral microbiota and oral cancer is still yet unclear.In the current study,the bacterial composition and functions that associated with oral cancer were investigated,and the relationship between microbial communities and epigenetic change was explored.Methods: We collected swab samples of oral cancer lesion and normal mucosa from 40 patients with OSCC.We tried to analyze the shifts of compositions and gene functions associated with OSCC by 16 S r RNA gene sequencing and metagenomic shotgun sequencing methods.Additionally,measurements of LINE-1 and CYP1A1 methylation by pyrosequencing technology were performed.Relationship between microbial subprofiles and gene hypermethylation were also explored.Results: In the current study,we found:(1)Significantly greater bacterial diversity was observed in the cancer samples than in the normal samples.In particular,a group of periodontitis-correlated taxa,including Fusobacterium,Dialister,Peptostreptococcus,Filifactor,Peptococcus,Catonella and Parvimonas,was significantly enriched in OSCC samples.Additionally,several operational taxonomic units(OTUs)associated with Fusobacterium were highly involved in OSCC and demonstrated good diagnostic power.(2)Candidate pathogens of periodontitis,Prevotella intermedia,Selenomonas sputigena and Filifactor alocis,were significantly enriched in the cancer.Microbiota functions exhibited remarkably different patterns in the cancer: The levels of flagellar assembly and iron uptake were remarkably higher in the cancer than in the control,and nitrite-reducing activity was lower.A series of virulence genes related to iron chelation,including ybt P,ybt Q,nrp A and nrp B,were also remarkably enriched in the cancer.(3)Methylation of LINE-1 showed no difference within the groups.The methylation of CYP1A1 promoter were significantly increased in OSCC samples,and positively correlated with the abundance of mycoplasma.Conclusions: Shift of oral microbial ecology is associated with OSCC.Compared with the control,the changes of microbial composition and functions presented a pro-inflammatory potential.Hypermethylation of specific genes associated with OSCC might be affected by the local microorganism,and warrant more studies.
Keywords/Search Tags:oral squamous cell carcinoma, high-throughput sequencing, metagenome, shotgun, hypermethylation
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