腸毒素脆弱擬桿菌與結(jié)直腸癌關(guān)系的研究
發(fā)布時間：2019-04-23 07:41
【摘要】：研究背景:人體腸道菌群可通過多種途徑影響腸道穩(wěn)態(tài),導(dǎo)致結(jié)直腸癌以及炎癥性腸病的發(fā)生。脆弱擬桿菌(Bacteroides fragilis,BF)為專性厭氧革蘭陰性短桿菌,是人體腸道共生菌。腸毒素脆弱擬桿菌ETBF(Enterotoxin bacteroides fragilis)能合成分泌一種脆弱擬桿菌毒素BFT(Bacteroid fragilis toxin),BFT可通過誘導(dǎo)激活Stat-3信號通路,上調(diào)IL-17的表達,誘發(fā)腸上皮內(nèi)瘤變的發(fā)生,從而促進結(jié)直腸癌的發(fā)生。研究發(fā)現(xiàn)ETBF在結(jié)直腸癌患者中的檢出增多,而且其陽性率隨著結(jié)直腸癌的腫瘤分期的增大而增加。但ETBF的致癌性仍缺乏足夠的流行病學(xué)證據(jù)支持。材料與方法:收集南方醫(yī)科大學(xué)南方醫(yī)院的腸鏡黏膜活檢或手術(shù)切除結(jié)直腸腫瘤的石蠟組織242例,分為輕度炎癥組50例、結(jié)直腸腺瘤組112例、結(jié)直腸癌組80例,收集臨床資料并對結(jié)直腸癌患者進行為時一年的隨訪。提取各組石蠟組織DNA,PCR檢測是否含有ETBF的特異性毒素基因bft,并分析ETBF與一些臨床指標(biāo)以及腫瘤預(yù)后指標(biāo)之間的關(guān)系。最后進行Phospho-Stat3與IL-17免疫組織化學(xué)染色。本實驗所用的統(tǒng)計學(xué)方法有:卡方檢驗、Mann-Whitney U檢驗、Kruska-Wallis H 檢驗。研究結(jié)果:結(jié)直腸腺瘤組與結(jié)直腸腺癌組的ETBF陽性率均明顯高于輕度炎癥組(p=0.008,p0.000),右半結(jié)腸的陽性率明顯高于左半結(jié)腸(X2=14.13,p0.000),ETBF陽性結(jié)直腸癌患者的TNM腫瘤分期明顯高于ETBF陰性患者(Z=-3.322,p=0.001)。ETBF陽性與陰性組之間的白細胞計數(shù)(WBC)、淋巴細胞計數(shù)(LYM)、中性粒細胞計數(shù)(NEU)、單核細胞計數(shù)(MO)均無明顯差異(p0.05);ETBF陽性組CRP定量、CEA定量明顯高于ETBF陰性組(p0.000,p=0.027)。ETBF陽性患者的淋巴結(jié)(Z=-2.892,p=0.004)與遠處轉(zhuǎn)移(Z=-2.881,p=0.004)均明顯嚴(yán)重于陰性患者。ETBF是否陽性與腫瘤患者一年內(nèi)是否復(fù)發(fā)或否死亡無明顯差異(X2=3.878,p=0.078;x2 =3.374,p=0.151),而ETBF陽性組的化療臨床獲益明顯差于陰性組(X2=5.437,p=0.020);ETBF陽性組的無瘤生存率明顯低于陰性組(X2 =12.836,p0.000)。輕度炎癥組ETBF感染與Stat3磷酸化為中等程度相關(guān)聯(lián),其余兩組無明顯關(guān)聯(lián)。結(jié)直腸腺瘤組中,ETBF陽性樣本IL-17表達水平下降(p=0.011)。結(jié)論:1、結(jié)直腸腫瘤的ETBF陽性率明顯升高,而且腫瘤TNM分期越靠近晚期,ETBF陽性率越高。2、ETBF陽性患者的腫瘤浸潤深度與遠處轉(zhuǎn)移均明顯嚴(yán)重于陰性患者;ETBF陽性組的化療療效明顯差于陰性組;ETBF陽性組的無瘤生存率也更低。因此ETBF陽性的結(jié)直腸癌患者預(yù)后更差。3、在結(jié)直腸輕度炎癥患者中,ETBF感染與Stat3磷酸化有一定關(guān)聯(lián),但在結(jié)直腸腫瘤患者中關(guān)聯(lián)性不大。ETBF陽性的結(jié)直腸腫瘤中,Stat3磷酸化以及IL-17的表達并無明顯升高,ETBF除了誘導(dǎo)Stat3磷酸化來促進TH17炎癥反應(yīng)之外可能還存在其他促癌機制。
[Abstract]:Background: human intestinal flora can affect intestinal homeostasis in many ways, leading to colorectal cancer and inflammatory bowel disease. Bacteroides fragilis (Bacteroides fragilis,BF) is a specific anaerobic gram-negative brevibacterium, which is a symbiotic bacteria in human intestinal tract. Enterotoxin ETBF (Enterotoxin bacteroides fragilis) can synthesize and secrete a fragile mycotoxin BFT (Bacteroid fragilis toxin), BFT, which can activate Stat-3 signaling pathway, up-regulate the expression of IL-17 and induce intestinal intraepithelial neoplasia. Thus promote the occurrence of colorectal cancer. It was found that ETBF was detected more frequently in colorectal cancer patients, and its positive rate increased with the increase of tumor stage. However, the carcinogenicity of ETBF is still not supported by enough epidemiological evidence. Materials and methods: a total of 242 paraffin-embedded tissues from Southern Hospital of Southern Medical University were divided into mild inflammation group (n = 50), colorectal adenomas group (n = 112) and colorectal cancer group (n = 80). The clinical data were collected and the patients with colorectal cancer were followed up for one year. DNA,PCR was extracted from paraffin-embedded tissues to detect the specific toxin gene bft, containing ETBF and the relationship between ETBF and some clinical indexes as well as tumor prognosis indexes was analyzed. Finally, immunohistochemical staining of Phospho-Stat3 and IL-17 was performed. The statistical methods used in this experiment are: Chi-square test, Mann-Whitney U test and Kruska-Wallis H test. Results: the positive rate of ETBF in colorectal adenomatosis and colorectal adenocarcinoma group was significantly higher than that in mild inflammatory group (p = 0.008, p0.000), and the positive rate in right colon was significantly higher than that in left colon (X2, 14.13, p0.000), and the positive rate in right colon was significantly higher than that in left colon (P < 0.001). The TNM staging in patients with ETBF positive colorectal cancer was significantly higher than that in patients with ETBF negative (Z = 3.322, p < 0.001). White blood cell count (WBC), lymphocyte count (LYM), neutrophil count (NEU), between positive and negative patients with ETBF was found to be significant higher than that in ETBF negative patients (P < 0.01). There was no significant difference in monocyte count (MO) (p0.05). The quantity of CRP and CEA in the ETBF positive group was significantly higher than that in the ETBF negative group (p0.000, p = 0.027). The lymph nodes and distant metastasis of the patients with positive ETBF were significantly higher than those in the ETBF negative group (P < 0.001, p = 0.004) and distant metastasis (P < 0.01, P < 0.01). There was no significant difference between the positive rate of ETBF and the recurrence or death of the tumor patients within one year (X2 / 3.878, p = 0.078). X2 = 3.374, p = 0.151), but the tumor-free survival rate of ETBF positive group was significantly lower than that of negative group (X2 = 12.836, p0.000), but the tumor-free survival rate of positive group was significantly lower than that of negative group (X2 = 5.437, p0.020); ETBF positive group). ETBF infection was associated with moderate phosphorylation of Stat3 in mild inflammatory group, but no significant correlation was found between the other two groups. In colorectal adenomas group, the expression level of IL-17 in ETBF positive samples was decreased (p < 0. 011). Conclusion: 1. The positive rate of ETBF in colorectal carcinoma was significantly higher, and the closer to the late stage of TNM stage, the higher the positive rate of ETBF. 2. The depth of invasion and distant metastasis in patients with positive tumor were more serious than those in patients with negative tumor. The chemotherapy efficacy of ETBF positive group was significantly lower than that of negative group, and the tumor-free survival rate of ETBF positive group was also lower. Therefore, the prognosis of patients with ETBF positive colorectal cancer is worse. 3. In patients with mild colorectal inflammation, ETBF infection is associated with phosphorylation of Stat3, but not in patients with colorectal cancer. The phosphorylation of Stat3 and the expression of IL-17 did not increase significantly. Besides inducing Stat3 phosphorylation to promote the inflammatory response of TH17, ETBF may also have other carcinogenic mechanisms.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R735.34
本文編號：2463259
[Abstract]:Background: human intestinal flora can affect intestinal homeostasis in many ways, leading to colorectal cancer and inflammatory bowel disease. Bacteroides fragilis (Bacteroides fragilis,BF) is a specific anaerobic gram-negative brevibacterium, which is a symbiotic bacteria in human intestinal tract. Enterotoxin ETBF (Enterotoxin bacteroides fragilis) can synthesize and secrete a fragile mycotoxin BFT (Bacteroid fragilis toxin), BFT, which can activate Stat-3 signaling pathway, up-regulate the expression of IL-17 and induce intestinal intraepithelial neoplasia. Thus promote the occurrence of colorectal cancer. It was found that ETBF was detected more frequently in colorectal cancer patients, and its positive rate increased with the increase of tumor stage. However, the carcinogenicity of ETBF is still not supported by enough epidemiological evidence. Materials and methods: a total of 242 paraffin-embedded tissues from Southern Hospital of Southern Medical University were divided into mild inflammation group (n = 50), colorectal adenomas group (n = 112) and colorectal cancer group (n = 80). The clinical data were collected and the patients with colorectal cancer were followed up for one year. DNA,PCR was extracted from paraffin-embedded tissues to detect the specific toxin gene bft, containing ETBF and the relationship between ETBF and some clinical indexes as well as tumor prognosis indexes was analyzed. Finally, immunohistochemical staining of Phospho-Stat3 and IL-17 was performed. The statistical methods used in this experiment are: Chi-square test, Mann-Whitney U test and Kruska-Wallis H test. Results: the positive rate of ETBF in colorectal adenomatosis and colorectal adenocarcinoma group was significantly higher than that in mild inflammatory group (p = 0.008, p0.000), and the positive rate in right colon was significantly higher than that in left colon (X2, 14.13, p0.000), and the positive rate in right colon was significantly higher than that in left colon (P < 0.001). The TNM staging in patients with ETBF positive colorectal cancer was significantly higher than that in patients with ETBF negative (Z = 3.322, p < 0.001). White blood cell count (WBC), lymphocyte count (LYM), neutrophil count (NEU), between positive and negative patients with ETBF was found to be significant higher than that in ETBF negative patients (P < 0.01). There was no significant difference in monocyte count (MO) (p0.05). The quantity of CRP and CEA in the ETBF positive group was significantly higher than that in the ETBF negative group (p0.000, p = 0.027). The lymph nodes and distant metastasis of the patients with positive ETBF were significantly higher than those in the ETBF negative group (P < 0.001, p = 0.004) and distant metastasis (P < 0.01, P < 0.01). There was no significant difference between the positive rate of ETBF and the recurrence or death of the tumor patients within one year (X2 / 3.878, p = 0.078). X2 = 3.374, p = 0.151), but the tumor-free survival rate of ETBF positive group was significantly lower than that of negative group (X2 = 12.836, p0.000), but the tumor-free survival rate of positive group was significantly lower than that of negative group (X2 = 5.437, p0.020); ETBF positive group). ETBF infection was associated with moderate phosphorylation of Stat3 in mild inflammatory group, but no significant correlation was found between the other two groups. In colorectal adenomas group, the expression level of IL-17 in ETBF positive samples was decreased (p < 0. 011). Conclusion: 1. The positive rate of ETBF in colorectal carcinoma was significantly higher, and the closer to the late stage of TNM stage, the higher the positive rate of ETBF. 2. The depth of invasion and distant metastasis in patients with positive tumor were more serious than those in patients with negative tumor. The chemotherapy efficacy of ETBF positive group was significantly lower than that of negative group, and the tumor-free survival rate of ETBF positive group was also lower. Therefore, the prognosis of patients with ETBF positive colorectal cancer is worse. 3. In patients with mild colorectal inflammation, ETBF infection is associated with phosphorylation of Stat3, but not in patients with colorectal cancer. The phosphorylation of Stat3 and the expression of IL-17 did not increase significantly. Besides inducing Stat3 phosphorylation to promote the inflammatory response of TH17, ETBF may also have other carcinogenic mechanisms.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R735.34
【參考文獻】
中國期刊全文數(shù)據(jù)庫 前1條
1 王建成;許淑珍;;產(chǎn)腸毒素脆弱類桿菌聚合酶鏈反應(yīng)檢測[J];胃腸病學(xué);2007年03期
，本文編號：2463259
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