壳多糖酶3样蛋白1在原发性肝癌中的检测及其临床价值  

The expression and clinical value of CHI3L1 in hepatocellular carcinoma

作　　者：饶春美 房萌 洪松 沈佳斌 蒋倩倩 张洁 高春芳 Rao Chunmei;Fang Meng;Hong Song;Shen Jiabin;Jiang Qianqian;Zhang Jie;Gao Chunfang(Department of Laboratory Medicine,Third Affiliated Hospital of Naval Medical University,Shanghai 200438,China)

机构地区：[1]海军军医大学第三附属医院检验科,上海200438

出　　处：《中华检验医学杂志》2020年第7期725-731,共7页Chinese Journal of Laboratory Medicine

基　　金：国家科技重大专项(2018ZX10302205);上海市卫健委协同创新集群(2019CXJQ03)。

摘　　要：目的:通过研究壳多糖酶3样蛋白1(CHI3L1)在原发性肝细胞癌(HCC)外周血、肝癌及配对癌旁组织中的表达水平,探讨CHI3L1在辅助原发性HCC临床管理中的价值。方法:回顾性研究。纳入2013至2017年在海军军医大学第三附属医院就诊的HCC患者405例,同时纳入肝硬化患者112例、正常体检(NC)者114例分别作为疾病和健康对照,酶联免疫法(ELISA)检测外周血CHI3L1蛋白水平。收集经病理确诊为原发性肝癌患者的肿瘤组织及配对癌旁组织90对,制成组织芯片,应用免疫组化染色分析HCC患者组织中CHI3L1的表达情况。采用Mann-Whitney U检验或Kruskal Wallis H检验比较各组差异,相关性分析采用Pearson双变量相关分析,癌组织和癌旁组织比较采用配对秩和检验。结果:外周血中肝硬化组、HCC组、NC组CHI3L1蛋白中位数(四分位数)分别为195.8(103.3,330.4)、118.2(74.9,201.0)及46.8(30.7,66.4)μg/L,肝硬化组CHI3L1蛋白水平显著高于HCC组和正常对照组(Z=5.186、12.928,P均<0.001),HCC组CHI3L1蛋白水平显著高于正常对照组(Z=10.788,P<0.001),HCC组中CHI3L1水平与是否合并肝硬化无关(Z=-0.286,P=0.775);血清CHI3L1水平与肝纤维化相关标志物[透明质酸(HA)、Ⅲ型前胶原N端肽(PⅢNP)、Ⅳ型胶原蛋白(Ⅳ-C)、FIB-4指数]呈正相关(r=0.202、0.159、0.299、0.221,P均<0.05),与白蛋白(ALB)呈负相关(r=-0.326,P<0.05),与丙氨酸氨基转移酶(AST)、凝血酶原时间(PT)呈正相关(r=0.138、0.160,P均<0.05),与肿瘤直径呈正相关(r=0.284,P<0.05),与中国肝癌的分期方案分期(CNLC)分期相关[晚期组CHI3L1水平为125.2(81.9,228.5)μg/L,高于早期组的112.0(70.2,169.2)μg/L(Z=-2.326,P=0.018)],而与微血管侵犯(Z=-1.531)、肿瘤包膜(χ^2=0.818)无明显相关关系(P均>0.05)。73对HCC组织标本中,癌组织CHI3L1表达阳性率为78%(57/73),癌旁组织CHI3L1表达阳性率为83%(61/73),配对分析比较癌组织中染色强度评分1.5(1.5,2.0)和癌旁组织染色强度�Objective To investigate the clinical management value of chitinase 3-like 1 protein(CHI3L1)in hepatocellular carcinoma(HCC)by studying the expression of CHI3L1 in peripheral blood,liver cancer and paired adjacent non-tumor tissues.Methods Retrospective study.From 2013 to 2017,405 patients with HCC in Third Affiliated Hospital of Naval Medical University were enrolled into the study.Meanwhile,112 patients with liver cirrhosis(LC),114 health subjects were included as disease and health controls.CHI3L1 in peripheral blood was detected by ELISA kit.Tissues array was made by collecting 90 pairs of tumor tissues and matched paracancer tissues,from HCC patients who were conformed by pathology.The expression of CHI3L1 in HCC tissues was analyzed by immunohistochemistry.Differences between independent groups were tested by Mann-Whitney U test or Kruskal Wallis H test,Pearson correlation analysis was used for analyzing the relationship between two subjects,and matched rank sum test was used for cancer tissue and adjacent tissue comparison.Results The median(quartile)of CHI3L1 protein in LC group,HCC group and NC group was 195.8(103.3,330.4)μg/L,118.2(74.9,201.0)μg/L,46.8(30.7,66.4)μg/L independently.The protein level of CHI3L1 in LC group was significantly higher than that in HCC group and health control group(Z=5.186,12.928,P<0.001).HCC group was significantly higher than that in health control group(Z=10.788,P<0.001).The level of CHI3L1 in HCC group was not related to whether liver cirrhosis was accompanied(Z=-0.286,P=0.775).The level of serum CHI3L1 was positively correlated with noninvasive fibrosis markers(HA,PⅢNP,Ⅳ-C,FIB-4 index)(r=0.202,0.159,0.299 and 0.221,P<0.05)and negatively correlated with ALB(r=-0.326,P<0.05)while positively correlated with AST and PT(r=0.138,0.160,P<0.05).Positively correlation was observed between CHI3L1 and tumor size(r=0.284,P<0.001).CNLC stage[CHI3L1 level in advanced group125.2(81.9,228.5)μg/L was higher than that in early group112.0(70.2,169.2)μg/L(Z=-2.326,P=0.018)],but no c

关 键 词：肝肿瘤 癌 肝细胞 壳多糖酶3样蛋白质1 肿瘤分期 组织阵列分析 

分 类 号：R735.7[医药卫生—肿瘤]