人脑星型胶质细胞瘤CYGB和p-ERK1/2及HIF-1α表达与临床病理特征和预后的关系  

Expressions of CYGB,phospho-ERK1/2 and HIF-1α in association with the pathological features and prognosis of astrocytic tumors

作　　者：杨叶 冯江龙 潘强锋 张梦琪 章俊 YANG Ye;FENG Jiang-long;PAN Qiang-feng;ZHANG Meng-qi;ZHANG Jun(Department of Pathology,Guizhou Medical University,Guiyang 550001,China;Department of Pathology,Affiliated Hospital of Guizhou Medical University,Guiyang 550001,China)

机构地区：[1]贵州医科大学病理学教研室,贵州贵阳550001 [2]贵州医科大学附属医院病理科,贵州贵阳550001

出　　处：《中华肿瘤防治杂志》2021年第19期1462-1470,共9页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金(82060565,81860554)。

摘　　要：目的探讨细胞红蛋白(CYGB)、磷酸化的细胞外调节蛋白激酶(p-ERK1/2)及缺氧诱导因子1(HIF-1α)在人脑星形胶质细胞瘤中的表达与临床病理特点、肿瘤发生机制、治疗耐受及预后的关系。方法选取贵州医科大学附属医院2014-01-01-2018-08-30经病理确诊的120例Ⅰ~Ⅳ级星形胶质细胞瘤和20例脑出血患者病理组织标本。采用免疫组化法检测星形胶质细胞瘤中CYGB、p-ERK1/2和HIF-1α的表达;随访患者术后2年生存率;分析其与临床病理分级、分子遗传学表型及与预后的关系。结果CYGB的阳性率(Ⅰ级为70.0%,Ⅱ级为61.7%,Ⅲ级为46.4%,Ⅳ级为31.8%)随星形胶质细胞瘤分级升高而降低,χ^(2)=30.241,P=0.001;而p-ERK1/2(Ⅰ级为30.0%,Ⅱ级为39.1%,Ⅲ级为57.1%,Ⅳ级为65.9%)和HIF-1α(Ⅰ级为40.0%,Ⅱ级为50.0%,Ⅲ级为64.3%,Ⅳ级为77.3%)的阳性率随星形胶质细胞瘤分级升高而增加,χ^(2)值分别为17.143和23.578,P值分别为0.006和0.001。CYGB阳性患者2年生存率高于阴性患者(χ^(2)=13.617,P=0.001),而p-ERK1/2(χ^(2)=7.656,P=0.006)和HIF-1α(χ^(2)=11.305,P=0.001)阳性患者则低于阴性患者;此外CYGB阳性表达与p-ERK1/2(r=-0.315,P=0.001)和HIF-1α(r=-0.317,P=0.001)的阳性表达呈低度负相关。进一步发现CYGB的阳性表达与异柠檬酸脱氢酶1(IDH1)R132H突变呈负相关,r=-0.368,P=0.032;p-ERK1/2阳性表达与DNA修复酶O^(6)-甲基鸟嘌呤-DNA甲基转移酶(MGMT)的阳性表达呈正相关,r=0.408,P=0.016。Cox回归分析显示,CYGB低表达、p-ERK1/2和HIF-1α高表达是星形胶质细胞瘤的高病理分级及不良预后的高风险因素,HR分别为0.339、1.979和2.522,95%CI分别为0.236~0.674、1.186~3.303和1.412~4.506,P值分别为0.001、0.009和0.002。结论CYGB低表达与星形胶质细胞瘤的高级别病理分级及不良预后密切相关。与调控肿瘤细胞增殖的ERK1/2蛋白活化、缺氧感受蛋白HIF-1α的稳定以及IDH1的突变呈负相关。提示CYGB在星形胶质细胞瘤可�Objective To investigate the expressions of cytoglobin(CYGB),phosphorylated extracellular regulatory protein kinase(p-ERK1/2)and hypoxia-induced factor-1α(HIF-1α)in human brain astrocytoma and the correlations with the pathological features,tumorigenesis,therapeutic resistance and prognosis.Methods Totally 120cases of human brain astrocytoma(GradeⅠ-Ⅳ)were collected from the Affiliated Hospital of Guizhou Medical University from January 1,2014to August 30,2018.The expressions of CYGB,P-ERK1/2and HIF-1αin astrocytoma were detected using immunohistochemistry.The 2-year survival rates were followed.The correlations of CYGB,P-ERK1/2and HIF-1αexpression with the pathological grading,epigenetic characters and prognosis were analyzed.Results CYGB expression(70.0%for gradeⅠ,61.7%for gradeⅡ,46.4%for gradeⅢ,and 31.8%for gradeⅣ)was negatively associated with the high grading of astrocytoma(χ^(2)=30.241,P=0.001),whereas the expressions of p-ERK1/2(30.0%for gradeⅠ,39.1%for gradeⅡ,57.1%for gradeⅢ,65.9%for gradeⅣ)and HIF-1α(40.0%for gradeⅠ,50.0%for gradeⅡ,64.3%for gradeⅢ,and77.3%for level four)were positively associated with the high grading of astrocytoma(χ^(2)=17.143,P=0.009;χ^(2)=23.578,P=0.001).The 2-year survival rate of patients with CYGB high-expression was higher than that of the patients with CYGB low-expression,whereas the 2-year survival rates of patients with p-ERK1/2or HIF-1αhigh-expressions were lower than that of the patients with p-ERK1/2or HIF-1αlow-expressions(χ^(2)=13.617,P=0.001;χ^(2)=7.656,P=0.006;χ^(2)=11.305,P=0.001).In addition,CYGB positive-expression was negatively associated with p-ERK1/2or HIF-1αpositive-expression(r=-0.315,P=0.001;r=-0.317,P=0.001).A further study showed that CYGB positive-expression was negatively associated with isocitrate dehydrogenase variant R132H (IDH1R132H)(r=-0.368,P=0.032),whereas p-ERK1/2positive-expression was positively associated with O^(6)-methylguanine-DNA methyltransferase(MGMT)positive-expression(r=0.408,P=0.016).Cox regression

关 键 词：细胞红蛋白 磷酸化的细胞外调节蛋白激酶 缺氧诱导因子1 星形胶质细胞瘤 临床病理联系 预后 

分 类 号：R739.41[医药卫生—肿瘤]