食管腺癌早期多种标志物检测试剂的开发与验证  

Early-stage multi-marker assay development and validation for esophageal adenocarcinoma

作　　者：赵刘诺贝 张晓梅 许萌 贾岩 陈浩[4] 杨靖 于晓波[2] ZHAO-LIU Nuobei;ZHANG Xiaomei;XU Meng;JIA Yan;CHEN Hao;YANG Jing;YU Xiaobo(School of Chemistry and Materials Science,Hebei University,Baoding 071002,China;State Key Laboratory of Medical Proteomics,Beijing Proteome Research Center,National Center for Protein Sciences Beijing(Phoenix Center),Beijing Institute of Lifeomics,Beijing 102206,China;Dansheng(Beijing)Epidemiology Technology Co.,Ltd.,Beijing 102206,China;South China State Key Laboratory of Cancer,Sun Yat Sen University Cancer Center,Sun Yat sen University Cancer Center,Guangzhou 510060,China)

机构地区：[1]河北大学化学与材料科学学院,保定071002 [2]医学蛋白质组学全国重点实验室,北京蛋白质组研究中心,国家蛋白质科学中心-北京(凤凰中心),军事科学院军事医学研究院生命组学研究所,北京102206 [3]旦生(北京)医学科技有限责任公司,北京102206 [4]华南肿瘤国家重点实验室,中山大学肿瘤医学合作创新中心,中山大学癌症中心,广州510060

出　　处：《中国免疫学杂志》2025年第4期972-978,共7页Chinese Journal of Immunology

基　　金：北京市自然科学基金(L234034);国家重点研发计划(2022YFE0210400);北京市科技计划(Z231100002723004);广东省基础与应用基础研究基金自然科学基金(2024A1515011958)。

摘　　要：目的:鉴于食管腺癌(EAC)现有临床标志物在早期诊断能力上的不足,本研究采用液相芯片技术开发多种血清蛋白标志物检测试剂,并初步验证这些标志物对于EAC的检测能力。方法:收集48例EAC患者和同期33例健康对照(HC)血清样本,通过液相芯片技术分析患者血清中鳞状细胞癌抗原(SCCA)、人细胞角蛋白19片段(Cyfra21-1)、肝细胞生长因子(HGF)和IL-8水平差异,通过受试者工作特征(ROC)曲线评估单一指标和4个指标联合的诊断效能。结果:SCCA、Cyfra21-1、HGF和IL-8检测范围分别为0.24~1000 ng/ml、45.72~100000 pg/ml、21.95~16000 pg/ml和0.61~10000 pg/ml。液相芯片技术与临床化学发光免疫技术(r=0.9494,P<0.0001)和ELISA技术(r=0.9551,P<0.0001)均有强相关性。与HC组相比,EAC组血清中SCCA和HGF显著升高(P<0.01),IL-8显著降低(P<0.05),Cyfra21-1差异无统计学意义(P>0.05)。在早期EAC组血清中HGF显著高于HC组(P<0.01)。ROC曲线显示,单个指标中HGF对早期EAC的诊断效能最佳,曲线下面积(AUC)为0.761,4项标志物组合的AUC为0.857,均优于临床标志物SCCA(AUC=0.604)和Cyfra21-1(AUC=0.515)。结论:液相芯片技术被用于联合检测人血清中SCCA、Cyfra21-1、HGF和IL-8,在EAC早期诊断中,4种标志物联合使用的诊断效能优于临床常用的肿瘤标志物SCCA和Cyfra21-1,这得益于液相芯片技术的高通量和高灵敏度特点。因此,这种联合检测方法具有较高的临床应用推广价值,有望为EAC的早期诊断提供更为准确和可靠的工具。Objective:Given the insufficiency of current clinical biomarkers for early diagnosis of esophageal adenocarcinoma(EAC),this study developed a panel of serum protein biomarker assays using liquid-phase chip technology and preliminarily validated the detection capabilities of these markers for EAC.Methods:Collected serum samples from 48 patients with EAC and 33 agematched healthy controls(HC).The levels of squamous cell carcinoma antigen(SCCA),human cytokeratin 19 fragment(Cyfra21-1),hepatocyte growth factor(HGF)and IL-8 in serum were analyzed by liquid chip technology.The diagnostic efficacy of a single indicator and a combination of four indicators were evaluated by receiver operation characteristic(ROC)curve.Results:The detection ranges of SCCA,Cyfra21-1,HGF and IL-8 were 0.24~1000 ng/ml,45.72~100000 pg/ml,21.95~16000 pg/ml,and 0.61~10000 pg/ml,respectively.The liquid chip technology shows a strong correlation with clinical chemiluminescence immunoassay(r=0.9494,P<0.0001)and ELISA technology(r=0.9551,P<0.0001).Compared to the HC group,serum levels of SCCA and HGF were significantly elevated in the EAC group(P<0.01),IL-8 was significantly decreased(P<0.05),while Cyfra21-1 shows no significant difference(P>0.05).In the early EAC group,serum HGF was significantly higher than in the HC group(P<0.01).ROC curve analysis shows that among individual markers,HGF exhibits the best diagnostic efficacy for early EAC with an area under the curve(AUC)of 0.761,while the AUC for the combination of the four biomarkers was 0.857,both superior to the clinical biomarkers SCCA(AUC=0.604)and Cyfra21-1(AUC=0.515).Conclusion:Liquid chip technology is used to jointly detect SCCA,Cyfra21-1,HGF,and IL-8 in human serum.In the early diagnosis of EAC,the diagnostic efficacy of the combined use of these four biomarkers is superior to that of the commonly used clinical tumor markers SCCA and Cyfra21-1.This advantage stems from the high throughput and high sensitivity characteristics of liquid-phase chip technology.Consequently,this combined de

关 键 词：食管腺癌 液相芯片 早期蛋白标志物 体外诊断 

分 类 号：R392.33[医药卫生—免疫学]