叶酸代谢等相关基因甲基化与哈萨克族食管癌及预后关系的研究

发布时间：2018-04-16 18:16

  本文选题：叶酸代谢 + DNA甲基化　； 参考：《新疆医科大学》2017年硕士论文

【摘要】：目的:探讨叶酸代谢相关基因MTHFR、CBS和肿瘤密切相关基因MGMT、P16、FHIT、RASSF1A甲基化状态与哈萨克族食管癌的关系,分析影响哈萨克族食管癌患者预后的因素,旨在为新疆哈萨克族食管癌防治提供依据。方法:收集2010-2015年间新疆哈萨克族食管癌患者192例,非食管癌对照200例,离子捕捉免疫分析法(Ion capture immunoassay,ICIA)测定血清叶酸水平,甲基化特异性聚合酶链反应(methylation specific PCR,MSP)技术检测其外周血中MTHFR、CBS、MGMT、P16、FHIT及RASSF1A基因启动子区甲基化水平,Log-rank检验和Cox比例风险回归模型(Cox’s proportional hazards regression model,简称Cox模型)分析哈萨克族食管癌预后因素。结果:1.病例组血清叶酸水平低于对照组(Z=—9.13,P=0.000),差异有统计学意义;2.基因甲基化水平分析:病例组MTHFR、CBS、MGMT、P16、FHIT及RASSF1A基因的甲基化率均高于对照组,差异均有统计学意义(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.基因甲基化与临床病理特征的关系:MTHFR基因甲基化与食管癌的性别、年龄和病理分型(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基因甲基化与食管癌的病理分型、浸润程度和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基因甲基化与食管癌的肿瘤大小、分化程度、区域淋巴结转移和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基因甲基化与食管癌的分化程度、浸润程度和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基因甲基化与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基因甲基化与食管癌的分化程度、区域淋巴结转移和TNM分期(χ~2=4.123,P=0.042;χ~2=14.884,P=0.000;χ~2=6.709,P=0.035),差异均有统计学意义。4.多因素Cox回归分析显示:肿瘤浸润程度(χ~2=7.961,P=0.005)、区域淋巴结转移(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)是影响食管癌预后的独立危险因素,女性性别(χ~2=4.981,P=0.026)和血清叶酸(χ~2=8.794,P=0.003;χ~2=8.165,P=0.004;χ~2=5.130,P=0.024)是食管癌预后的保护因素。结论:MTHFR、CBS、MGMT、P16、FHIT及RASSF1A基因甲基化均与新疆哈萨克族食管癌的发生密切相关,肿瘤浸润程度、区域淋巴结转移、TNM分期、CBS和RASSF1A基因甲基化是影响食管癌预后的独立危险因素,女性性别和血清叶酸是保护因素。
[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).娴告鼎绋嬪害鍜孴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�＄檶鐨勭梾鐞嗗垎鍨嬪拰TNM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�＄檶鐨勫垎鍖栫▼搴�,鍖哄煙娣嬪反缁撹浆绉诲拰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�寮傚潎鏈夌粺璁″�︽剰涔，

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