The Effect Of Enterotoxin Bacteroides Fragilis Infection On Colorectal Cancer

Background:The human intestinal flora can impact the homeostasis of gastrointestinal tract in various pathways,which may induce colon carcinogenesis or inflammatory bowel disease.As one of the human intestinal commensal bacteria,Bacteroides fragilis is a typical anaerobic Gram-negative Brevibacterium.Bacteroides fragilis toxin(BFT)can be synthesized and secreted by enterotoxin bacteroides fragilis(ETBF).BFT can up-regulate the expression of IL-17 by inducing Stat-3 signaling pathway,and inducing intestinal intraepithelial neoplasia occurs,thus promoting the occurrence of colorectal cancer.It has been found that ETBF colonization increases in colorectal cancer patients,and its positive rate raises with colorectal cancer TNM staging.The carcinogenicity of ETBF still require more supporting epidemiological evidence.Materials and methods:242 cases of colorectal mucosa biopsy or resection,which had been made into paraffin tissue,were collected from Southern Medical University Affiliated Nanfang Hospital.These samples were divided into colorectal adenoma group(112 cases),colorectal cancer group(80 cases)and mild inflammation group(50 cases).Clinical data were collected from patients in groups and patients with colorectal cancer were followed up for one year.The DNA of each group of paraffin tissues was extracted and then the endotoxin gene segment of ETBF would be amplified by polymerase chain reaction.Then analyze the relationship between ETBF and some clinical indicators and tumor prognosis.Paraffin sections of each group were immunohistochemically stained with Phosphor-Stat3 and IL-17.The average optical density of IL-17 immunohistochemical staining,which was analysed by Image pro plus 6.0 software,was used as IL-17 expression.The statistical methods used in this study were chi-square test,Mann-Whitney U test,Kruska-Wallis H test.Results:The positive rate of ETBF in colorectal adenoma group and colorectal adenocarcinoma group was significantly higher than that in mild inflammation group(p=0.008,p<0.000).The positive rate of right colon was significantly higher than that of left colon(x2 = 14.13,P<0.000).TNM tumor staging in patients with ETBF-positive colorectal cancer was significantly higher than that in ETBF-negative patients(Z =-3.322,p = 0.001).There was no significant difference in WBC,lymphocyte count(LYM),neutrophil count(NEU)and monocyte count(MO)between ETBF positive and negative group(p>0.05).The positive rate of CRP in ETBF positive group was significantly higher than that in ETBF negative group(p<0.000),and ETBF positive group was also significantly higher than ETBF negative group(p = 0.027).The depth of tumor invasion(Z=-2.892,p=0.004)and distant metastasis of ETBF positive patients(Z=-2.881,p=0.004)were significantly worse in negative patients.Analysis of colorectal cancer patients with ETBF colonization and prognosis and the relationship between the efficacy of chemotherapy found whether ETBF colonization and tumor patients within one year of recurrence and whether there is no significant difference within one year(x2 =3.878,p=0.078;x2 =3.374,p=0.151).ETBF positive group of chemotherapy was significantly worse than the negative group(x2 =5.437,p=0.020).ETBF positive group of tumor-free survival rate was significantly lower than the negative group(x2 =12.836,p<0.000).In the mild inflammatory group,ETBF infection was moderatly associated with Stat3 phosphorylation,and there was no significant association between the other two groups.The expression of IL-17 in colorectal adenoma group and colorectal adenocarcinoma group was significantly lower than that in mild inflammation group(p<0.000).There was no significant difference in IL-17 expression between ETBF positive and negative samples(p = 0.307).Conclusion:1.The positive rate of ETBF in colorectal neoplasms was significantly higher,and the higher colorectal cancer TNM stage,the higher the positive rate of ETBF was.2.The tumor infiltration depth of ETBF positive patients and their distant metastasis were significantly worse than those with negative,and ETBF positive group of chemotherapy efficacy was significantly worse than the negative group.The tumor-free survival rate of ETBF positive group was significantly lower than that of negative group.Therefore,ETBF-positive colorectal cancer patients are with poor prognosis.3.There was certain association between ETBF infection and Stat3 phosphorylation in colorectal mild inflammation patients,but with little relevance in patients with colorectal neoplasm.In ETBF-positive colorectal tumors,Stat3 phosphorylation and IL-17 expression was not significantly increased.In addition to induce Stat3 phosphorylation to promote TH17 inflammatory response,ETBF may also exist other mechanisms of carcinogenesis.