人附睾蛋白4在肺癌诊疗中的应用价值  

Application value of human epididymis protein 4 in the diagnosis and treatment of lung cancer

作　　者：杨洋 倪凯茹[1] 高晨慧[1] 黄宏 石怡珍[1] Yang Yang;Ni Kairu;Gao Chenhui;Huang Hong;Shi Yizhen(Department of Nuclear Medicine,the Second Affiliated Hospital of Soochow University,Suzhou 215004,China;Department of Nuclear Medicine,Zhejiang Cancer Hospital,Hangzhou Institute of Medicine(HIM),Chinese Academy of Sciences,Hangzhou 310022,China)

机构地区：[1]苏州大学附属第二医院核医学科,苏州215004 [2]浙江省肿瘤医院核医学科、中国科学院杭州医学研究所,杭州310022

出　　处：《中华核医学与分子影像杂志》2024年第10期597-602,共6页Chinese Journal of Nuclear Medicine and Molecular Imaging

摘　　要：目的探究人附睾蛋白4(HE4)与传统肿瘤标志物相比,在肺癌诊疗中的临床价值及应用前景。方法前瞻性纳入2021年2月至2022年6月苏州大学附属第二医院的230例肺癌患者[男138例、女92例,年龄(61.1±12.3)岁]、96例肺部良性疾病患者[男62例、女34例,年龄(60.2±14.8)岁;其中良性占位组43例,肺部感染组53例]及60名健康者[男40名、女20名,年龄(62.8±11.4)岁],采用电化学发光法检测所有受试者血清HE4、癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)、细胞角蛋白19片段(CYFRA21-1)、胃泌素释放肽前体(ProGRP)及糖类抗原125(CA125)水平;采用免疫组织化学法检测其中55例肺癌患者肿瘤组织中HE4蛋白表达情况。采用χ2检验、Mann-WhitneyU检验、Kruskal-Wallis秩和检验及Bonferroni校正法分析数据。通过ROC曲线评估HE4及其他肿瘤标志物的诊断效能,不同AUC间的比较采用Delong检验。结果肺腺癌组织标本的HE4表达阳性率高于非腺癌[93.1%(27/29)和23.1%(6/26);χ2=28.01,P<0.001]。肺癌组血清HE4水平[70.70(51.93,109.05)pmol/L]高于良性占位组[59.80(48.20,73.50)pmol/L]及健康对照组[55.25(44.60,74.25)pmol/L],肺部感染组血清HE4水平[97.90(76.62,155.00)pmol/L]明显高于肺癌组[H=46.19,均P<0.008(Bonferroni校正法)]。血清HE4水平在不同年龄、性别、吸烟状况、分期及早期病理类型组间差异有统计学意义(z值:-5.07~9.83,均P<0.05)。ROC曲线分析示血清HE4诊断肺癌的最佳界值为79.22 pmol/L,其灵敏度和特异性分别41.30%(95/230)和83.33%(50/60),CA125与HE4表现出较高的诊断价值[AUCCA125(0.695)>AUCHE4(0.656)>AUCCEA(0.614)>AUCCYFRA21-1(0.599)>AUCProGRP(0.501)>AUCNSE(0.470)];6项肿瘤标志物联合诊断的AUC可达到0.750,诊断效能优于HE4(z=2.75,P=0.006)。结论肺腺癌组织HE4免疫组织化学呈高表达,血清HE4在肺占位的良恶性鉴别及患者病情评估中具有重要的临床应用价值。ObjectiveTo analyze the advantages of human epididymis protein 4(HE4)compared with traditional tumor markers in the diagnosis and treatment of lung cancer.MethodsFrom February 2021 to June 2022,230 lung cancer patients(138 males,92 females;age(61.1±12.3)years),96 benign lung disease patients(62 males,34 females;age(60.2±14.8)years;including 43 cases of lung benign placeholder and 53 cases of pulmonary infection),and 60 healthy volunteers(40 males,20 females;age(62.8±11.4)years)from the Second Affiliated Hospital of Soochow University were prospectively collected.Serum HE4,carcinoembryonic antigen(CEA),neuron-specific enolase(NSE),cytokeratin 19 fragment(CYFRA21-1),pro-gastrin-releasing peptide(ProGRP)and carbohydrate antigen(CA)125 were detected by electrochemical analysis.The expression of HE4 in tumor tissues of 55 patients with lung cancer was detected by immunohistochemical method.χ2 test,Mann-Whitney U test,Kruskal-Wallis rank sum test and Bonferroni correction method were used to analyze data.The diagnostic efficiencies of HE4 and other tumor markers were evaluated by ROC curve analysis and the difference of AUCs was analyzed by Delong test.ResultsThe positive expression rate of HE4 in adenocarcinoma tissue was significantly higher than that in non-adenocarcinoma tissue(93.1%(27/29)vs 23.1%(6/26);χ2=28.01,P<0.001).The level of serum HE4 in the lung cancer group(70.70(51.93,109.05)pmol/L)was significantly higher than that in the pulmonary benign placeholder group(59.80(48.20,73.50)pmol/L)and the healthy control group(55.25(44.60,74.25)pmol/L),and that in the pulmonary infection group(97.90(76.62,155.00)pmol/L)was higher than that in the lung cancer group(H=46.19,all P<0.008(Bonferroni correction method)).The levels of serum HE4 were significantly different in age,sex,smoking,disease stage and pathological types in early stage(z values:from-5.07 to 9.83,all P<0.05).The ROC curve analysis indicated that the optimal cut-off value of serum HE4 for diagnosing lung cancer was 79.22 pmol/L,with the sensitivity

关 键 词：肺肿瘤 生物标记 肿瘤 附睾分泌蛋白质类 

分 类 号：R734.2[医药卫生—肿瘤]