本文選題：葉酸代謝 + DNA甲基化��； 參考：《新疆醫(yī)科大學》2017年碩士論文

【摘要】：目的:探討葉酸代謝相關(guān)基因MTHFR、CBS和腫瘤密切相關(guān)基因MGMT、P16、FHIT、RASSF1A甲基化狀態(tài)與哈薩克族食管癌的關(guān)系,分析影響哈薩克族食管癌患者預后的因素,旨在為新疆哈薩克族食管癌防治提供依據(jù)。方法:收集2010-2015年間新疆哈薩克族食管癌患者192例,非食管癌對照200例,離子捕捉免疫分析法(Ion capture immunoassay,ICIA)測定血清葉酸水平,甲基化特異性聚合酶鏈反應(methylation specific PCR,MSP)技術(shù)檢測其外周血中MTHFR、CBS、MGMT、P16、FHIT及RASSF1A基因啟動子區(qū)甲基化水平,Log-rank檢驗和Cox比例風險回歸模型(Cox’s proportional hazards regression model,簡稱Cox模型)分析哈薩克族食管癌預后因素。結(jié)果:1.病例組血清葉酸水平低于對照組(Z=—9.13,P=0.000),差異有統(tǒng)計學意義;2.基因甲基化水平分析:病例組MTHFR、CBS、MGMT、P16、FHIT及RASSF1A基因的甲基化率均高于對照組,差異均有統(tǒng)計學意義(χ~2=45.144,P=0.000;χ~2=18.465,P=0.000;χ~2=11.853,P=0.003;χ~2=37.359,P=0.000;χ~2=46.608,P=0.000;χ~2=14.766,P=0.001);3.基因甲基化與臨床病理特征的關(guān)系:MTHFR基因甲基化與食管癌的性別、年齡和病理分型(χ~2=4.099,P=0.043;χ~2=12.800,P=0.005;χ~2=9.851,P=0.0 2 0)、C B S基因甲基化與食管癌的病理分型、浸潤程度和T N M分期(χ~2=24.463,P=0.000;χ~2=4.488,P=0.034;χ~2=6.412,P=0.041)、MGMT基因甲基化與食管癌的腫瘤大小、分化程度、區(qū)域淋巴結(jié)轉(zhuǎn)移和TNM分期(χ~2=5.424,P=0.020;χ~2=7.412,P=0.006;χ~2=6.692,P=0.010;χ~2=10.739,P=0.005)、P16基因甲基化與食管癌的分化程度、浸潤程度和TNM分期(χ~2=6.356,P=0.012;χ~2=10.478,P=0.001;χ~2=11.646,P=0.003)、FHIT基因甲基化與食管癌的病理分型和TNM分期(χ~2=15.479,P=0.001;χ~2=12.564,P=0.002)、RASSF1A基因甲基化與食管癌的分化程度、區(qū)域淋巴結(jié)轉(zhuǎn)移和TNM分期(χ~2=4.123,P=0.042;χ~2=14.884,P=0.000;χ~2=6.709,P=0.035),差異均有統(tǒng)計學意義。4.多因素Cox回歸分析顯示:腫瘤浸潤程度(χ~2=7.961,P=0.005)、區(qū)域淋巴結(jié)轉(zhuǎn)移(χ~2=16.135,P=0.000)、TNM分期(χ~2=4.789,P=0.029;χ~2=7.509,P=0.006)、CBS基因甲基化(χ~2=6.212,P=0.013)和RASSF1A基因甲基化(χ~2=6.355,P=0.012)是影響食管癌預后的獨立危險因素,女性性別(χ~2=4.981,P=0.026)和血清葉酸(χ~2=8.794,P=0.003;χ~2=8.165,P=0.004;χ~2=5.130,P=0.024)是食管癌預后的保護因素。結(jié)論:MTHFR、CBS、MGMT、P16、FHIT及RASSF1A基因甲基化均與新疆哈薩克族食管癌的發(fā)生密切相關(guān),腫瘤浸潤程度、區(qū)域淋巴結(jié)轉(zhuǎn)移、TNM分期、CBS和RASSF1A基因甲基化是影響食管癌預后的獨立危險因素,女性性別和血清葉酸是保護因素。
[Abstract]:Objective: to investigate the relationship between methylation status of folate metabolism-related gene MTHFRnCBS and MGMTTP-16FHIT-RASSF1A methylation in Kazakh esophageal carcinoma, and to analyze the factors influencing prognosis of Kazakh esophageal carcinoma.The aim is to provide basis for prevention and treatment of esophageal cancer in Kazak nationality in Xinjiang.Methods: serum folic acid levels were measured by Ion capture immunoassay (IIA) in 192 Kazak esophageal cancer patients and 200 non-esophageal cancer control patients from 2010 to 2015 in Xinjiang.Analysis of Kazakh nationality by methylation-specific polymerase chain reaction with methylation specific polymerase chain reaction (MSPs) technique to detect the methylation level of RASSF1A promoter region in the peripheral blood of Kazakh nationality by using the Cox proportional risk regression model (Cox model) and the Cox proportional risk regression model (Cox model) for detecting the methylation level of the promoter region of the MTHFRRX MGMTRHIT and the promoter region of the RASSF1A gene in the Kazakh nationality (Cox model for short), using the Log-rank test and the Cox proportional risk regression model.Prognostic factors of esophageal carcinoma.The result is 1: 1.The serum folic acid level in the case group was significantly lower than that in the control group.The relationship between methylation and clinicopathological characteristics of esophageal carcinoma: the relationship between methylation and sex, age and pathological type of esophageal carcinoma (蠂 ~ (2)) 4.099 (P) 0.043, 蠂 ~ (2 +) ~ (22) 12.800 (P) 0.005, 蠂 ~ (2) 9.851 (P = 0.020), methylation of C B / S gene and pathological typing of esophageal carcinoma.Degree of invasion and T N M staging (蠂 2 / 24. 463 / P = 0.000; 蠂 ~ (2) = 24.488 / P ~ (0.034)); methylation of MGMT gene and tumor size, differentiation, regional lymph node metastasis and TNM staging of esophageal carcinoma (蠂 ~ 2 / 2 = 24.463 / P ~ 0. 0020; 蠂 ~ 2 = 7.412 / P ~ 0. 006; 蠂 ~ 2 = 26 / 46.692P ~ 0. 010; 蠂 ~ 2 = 10. 739P = 0. 005P = 0. 005P = 0. 005P = 10. 739P = 10. 739P = 10. 739P).嫻告鼎紼嬪害鍜孴NM鍒嗘湡(蠂~2=6.356,P=0.012;蠂~2=10.478,P=0.001;蠂~2=11.646,P=0.003),FHIT鍩哄洜鐢插熀鍖栦笌椋熺鐧岀殑鐥呯悊鍒嗗瀷鍜孴NM鍒嗘湡(蠂~2=15.479,P=0.001;蠂~2=12.564,P=0.002),RASSF1A鍩哄洜鐢插熀鍖栦笌椋熺鐧岀殑鍒嗗寲紼嬪害,鍖哄煙娣嬪反緇撹漿縐誨拰TNM鍒嗘湡(蠂~2=4.123,P=0.042;蠂~2=14.884,P=0.000;蠂~2=6.709,P=0.035),宸紓鍧囨湁緇熻瀛︽剰涔，

本文編號：1760054