摘要
目的探讨原纤维蛋白-1(fibrillin-1,FBN1)基因甲基化及蛋白表达水平与肝豆状核变性患者临床病理特征及预后的关系。方法选取2013年2月至2016年2月79例肝豆状核变性患者肝病变组织为研究对象(肝豆状核变性组),选取其肝脏正常组织(距离病变组织>2 cm)作为正常对照组。采用直接测序法检测肝组织中FBN1基因甲基化水平,采用免疫组织化学法检测肝组织FBN1蛋白表达水平,收集患者年龄、性别、肝豆状核变性家族史、病程及天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、铜蓝蛋白(ceruloplasmin,CP)、尿铜(urine copper,u-Cu)水平等基线资料;采用卡方检验分析肝豆状核变性患者FBN1基因甲基化及蛋白表达水平与临床病理特征的关系;采用Kaplan-Meier法分析肝豆状核变性患者FBN1基因甲基化及蛋白表达水平与预后的关系;采用多因素Cox回归分析影响肝豆状核变性患者预后的因素。结果肝豆状核变性组FBN1蛋白阳性表达率显著高于正常对照组,而FBN1基因甲基化率显著低于正常对照组(P<0.05)。FBN1基因甲基化及蛋白表达与性别、病程及AST、ALT水平无相关性(P>0.05),与年龄、肝豆状核变性家族史及CP、u-Cu水平有相关性(P<0.05)。FBN1蛋白阳性表达肝豆状核变性患者5年生存率低于FBN1蛋白阴性表达患者(χ^(2)=6.269,P<0.05),而FBN1基因甲基化肝豆状核变性患者5年生存率高于FBN1基因非甲基化患者(χ^(2)=5.281,P<0.05)。FBN1蛋白阳性表达是影响肝豆状核变性患者死亡的独立危险因素(P<0.05),FBN1基因甲基化是影响肝豆状核变性患者死亡的保护因素(P<0.05)。结论FBN1基因非甲基化及蛋白高表达可能与肝豆状核变性的发生、发展及预后有关。
Objective To investigate the relationship between fibrillin-1(FBN1)gene methylation and protein expression levels and clinicopathological characteristics and prognosis of patients with hepatolenticular degeneration.Methods Seventy-nine liver disease tissues of patients with hepatolenticular degeneration from Feb.2013 to Feb.2016 were selected as the research objects(hepatolenticular degeneration group),and their normal liver tissues(>2 cm from diseased tissues)were selected as the normal control group.Direct sequencing method was used to detect the methylation level of FBN1 gene in liver tissue,immunohistochemical method was used to detect the expression level of FBN1 protein in liver tissue,the age,gender,family history of hepatolenticular degeneration,course of disease,and aspartate aminotransferase(AST),alanine aminotransferase(ALT),ceruloplasmin(CP),urine copper(u-Cu)and other baseline data of patients were collected;Chi-square test was used to analyze the relationship between FBN1 gene methylation,protein expression levels and clinicopathological characteristics in patients with hepatolenticular degeneration;Kaplan-Meier method was used to analyze the relationship between FBN1 gene methylation and protein expression levels and prognosis in patients with hepatolenticular degeneration;multivariate Cox regression analysis was used to analyze the factors affecting the prognosis of patients with hepatolenticular degeneration.Results The positive expression rate of FBN1 protein in hepatolenticular degeneration group was significantly higher than that in normal control group,while the methylation rate of FBN1 gene was significantly lower than that in normal control group(P<0.05).FBN1 gene methylation and protein expression were not correlated with sex,course of disease,AST and ALT levels(P>0.05),but with age,family history of hepatolenticular degeneration,CP and u-Cu levels(P<0.05).The 5-year survival rate of patients with FBN1 protein positive hepatolenticular degeneration was lower than that of patients with FBN1
作者
周显东
冉涛
高小燕
聂鑫
王永红
ZHOU Xiandong;RAN Tao;GAO Xiaoyan;NIE Xin;WANG Yonghong(Department of Laboratory Medicine,Qianjiang Central Hospital of Chongqing,Chongqing 409000;Department of Laboratory Medicine,Qianjiang Hospital of Traditional Chinese Medicine;Department of Experimental Medicine,West China Hospital,Sichuan University,China)
出处
《胃肠病学和肝病学杂志》
CAS
2022年第6期683-688,共6页
Chinese Journal of Gastroenterology and Hepatology
基金
重庆市黔江区科技计划项目(2017026)。
