急性髓系白血病中医证型与Dkk-3、Wif-1基因甲基化水平相关性研究  

A study on the correlation between TCM syndrome types and methylation levels of Dkk-3 and Wif-1 genes in the acute myeloid leukemia patient

作　　者：陈毅宁[1] 谢宝真 廖斌[1] 齐彦[1] 徐成波[1] 陈佳薇[1] 梁春灵 陈泽松 CHEN Yining

机构地区：[1]福建中医药大学附属人民医院,福建福州350004

出　　处：《中医临床研究》2023年第13期11-16,共6页Clinical Journal Of Chinese Medicine

基　　金：福建省中青年教师教育科研项目(JAT190245);中华中医药学会委托课题(202169-004)。

摘　　要：目的:研究急性髓系白血病(Acute Myeloid Leukemia,AML)患者不同中医证型与焦磷酸测序法检测的Dkk-3和Wif-1基因启动子甲基化水平的关系,比较不同证型Dkk-3和Wif-1基因甲基化水平与AML患者生存时间的差异,为AML中医辨证分型提供参考依据及评估预后。方法:选取45例2020年6月-2021年6月福建中医药大学附属人民医院血液病科门诊或住院初诊AML患者(病例组)和20例缺铁性贫血患者(对照组),比较焦磷酸测序法检测的两组Dkk-3、Wif-1基因甲基化表达水平差异,并比较组内气阴两虚证、瘀血痰结证、毒热炽盛证三种不同证型与Dkk-3和Wif-1基因启动子甲基化水平的关系,并以AML患者死亡或随访终点(1年)为终止时间点,比较各证型患者的生存时间差异。结果:AML患者中气阴两虚证者最多,瘀血痰结证者次之,毒热炽盛证者最少,各中医证型与性别、FAB分型、骨髓原始细胞比例的差异无统计学意义(P>0.05),但不同中医证型患者年龄的差异有统计学意义(P<0.05)。AML患者的Dkk-3、Wif-1基因甲基化表达水平均比对照组高,差异有统计学意义(P<0.01)。各证型AML患者Dkk-3基因甲基化表达水平的差异无统计学意义(P>0.05);各证型AML患者Wif-1基因甲基化表达水平的差异有统计学意义(P<0.05),气阴两虚证患者的表达水平最高,瘀血痰结证次之,毒热炽盛证最小。对AML患者进行随访,中位随访0.3~24个月,中位生存时间为(11.80±6.29)个月,各个证型患者总体生存时间的差异无统计学意义(P>0.05)。结论:AML患者的Dkk-3、Wif-1基因甲基化阳性率较无恶性血液病患者高,Dkk-3、Wif-1基因甲基化可能与AML发病有相关性。AML患者中医证型与Wif-1基因甲基化表达有相关性,气阴两虚证、瘀血痰结证患者的Wif-1甲基化表达明显高于毒热炽盛证患者,其可能可以作为AML中医辨证分型的参考指标。各中医证型AML患者生存时间的差异无统计学意义(Objective:To study the relationship between different TCM syndromes and the promoter methylation levels of Dkk-3 and Wif-1 genes detected by pyrosequencing in patients with acute myeloid leukemia(AML),and compare the differences between the methylation levels of differents types of Dkk-3 and Wif-1 genes and the survival time of AML patients,so as to provide a reference basis for TCM syndrome differentiation and prognosis assessment of AML.Methods:Forty-five newly diagnosed AML patients(the case group)and 20 iron-deficiency anemia patients(the control group)enrolled in the Hematology Department of The Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine from June 2020 to June 2021 were selected as research objects.The differences in the methylation expression levels of Dkk-3 and Wif-1 genes between the two groups were compared,and the relationships among three different syndrome types of the Qi and Yin deficiency syndrome(气阴两虚证),the blood stasis and phlegm coagulated syndrome and the excessive noxious heat syndrome and the promoter methylation levels of Dkk-3 and Wif-1 genes within each groups were compared.With the end point of death or followed-up(1 year)of AML patients as the termination time point,the difference of survival time among patients with different syndrome types was compared.Results:In AML patients,the cases of the Qi and Yin deficiency syndrome were the most,followed by the cases of the blood stasis and phlegm coagulated syndrome,and the cases of the excessive noxious heat syndrome were the least.There were no statistically significant differences between different TCM syndrome types and gender,FAB type,and bone marrow blast ratio of AML patients(P>0.05),but there was a statistically significant difference between different TCM syndrome types and age of AML patients(P<0.05).The methylation expression levels of Dkk-3 and Wif-1 genes in AML patients were higher than those in the control group,and the differences were statistically significant(P<0.01).There was

关 键 词：急性髓系白血病 中医证型 Dkk-3、Wif-1基因甲基化 总体生存时间 

分 类 号：R733.7[医药卫生—肿瘤]