CN112255408B - 一种肿瘤生物标志物及肿瘤检测试剂盒 - Google Patents

一种肿瘤生物标志物及肿瘤检测试剂盒 Download PDF

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CN112255408B
CN112255408B CN202011112080.1A CN202011112080A CN112255408B CN 112255408 B CN112255408 B CN 112255408B CN 202011112080 A CN202011112080 A CN 202011112080A CN 112255408 B CN112255408 B CN 112255408B
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孙延斌
闫水华
孟晨
曹文超
刘磊
刘艺
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Abstract

本发明公开了一种肿瘤生物标志物及肿瘤检测试剂盒，所述肿瘤生物标志物包括单核细胞趋化蛋白1(MCP‑1)、乳酸脱氢酶、层粘蛋白和CYFRA21‑1。本发明是通过综合使用四种肿瘤生物标志物，能够有效提高肾癌的检测特异性。

Description

一种肿瘤生物标志物及肿瘤检测试剂盒
技术领域
本发明属于医学检测领域，具体是一种肿瘤生物标志物及肿瘤检测试剂盒。
背景技术
肾癌是起源于肾实质泌尿小管上皮***的恶性肿瘤，学术名词全称为肾细胞癌，又称肾腺癌，简称为肾癌。肾癌是威胁人们健康的常见恶性肿瘤之一。我国肾癌的发病率近年来一直处于显著的上升趋势，其发病率年增长率高达5％，成为我国肿瘤发病率和死亡率增长最快的肿瘤之一。
早期肾癌局限于肾脏包膜内，5年生存期高达90％以上；但当肿瘤扩散到包膜外或远处转移时，肿瘤的治疗就相当困难且预后较差，5年生存期仅有15％左右。最近，虽然在健康诊断或其它疾病中接受超声波检查或CT检查时偶然被发现的情况增加，但是，依然认为是难以早期发现的癌。
生物标志物是指与身体的正常过程或病态过程、或者对治疗的药理学反应相关的生物体内的物质或图像数据，成为身体状态的客观指标。生物标志物包含生化学检查、血液检查、肿瘤标志物之类的所谓的临床检查值、CT或MRI之类的图像诊断数据等各种各样的标志物。特别是作为疾病的指标表示疾病的存在或分级的生物标志物在疾病的发现、诊断、预后预测等目前的诊疗中是不可缺少的。另外，在新药开发中，生物标志物在开发化合物的选择和评价中被利用。
大多数肾癌患者是由于健康查体时发现的无症状肾癌，这些患者占肾癌患者总数的50％～60％以上。有症状的肾癌患者中最常见的症状是腰痛和血尿，少数患者是以腹部肿块来院就诊。10％～40％的患者出现副瘤综合征，表现为高血压、贫血、体重减轻、恶病质、发热、红细胞增多症、肝功能异常、高钙血症、高血糖、血沉增快、神经肌肉病变、淀粉样变性、溢乳症、凝血机制异常等改变。20％～30％的患者可由于肿瘤转移所致的骨痛、骨折、咳嗽、咯血等症状就诊。因此，肾癌在许多情况下几乎没有症状，进入晚期后才被发现的情况占大半。更为重要的是，由于早期肾癌往往无临床症状，且临床上缺乏肾癌早期诊断分子标志物，有近30％的患者初诊即为晚期。因此，临床上亟需寻找到简便易行的分子标志物，以实现肾癌的早期诊断，从而提高肾癌患者的总体生存期。因此，急需寻找一些常规生化检测中就具有高灵敏度的标志物，为早期预示肾癌奠定基础。
发明内容
本发明的目的在于提供一种肾癌生物标志物及其诊断试剂盒，以解决上述背景技术中提出的问题。
为实现上述目的，本发明提供如下技术方案：
本发明一方面涉及一种肿瘤生物标志物，所述生物标志物包括单核细胞趋化蛋白1(MCP-1)、乳酸脱氢酶、层粘蛋白和CYFRA21-1中的至少一种，优选为至少三种，特别优选为全部四种；所述肿瘤是肾癌。
本发明所述的单核细胞趋化蛋白-1(monocyte chemotactic protein 1,MCP-1)又称bai单核细胞趋化和激活du因子(zhimonoctye chemotactic and activatingfactor,MCAF)，属于C-C亚族(β亚族)成员。MCP-1/MCAF起初是从人髓样单dao核细胞系THP-1、神经胶质瘤细胞系以及LPS或PHA刺激的人PBMC培养上清中发现。目前已知，单核细胞、巨噬细胞、成纤维细胞、内皮细胞、B细胞、平滑肌细胞等在PHA、LPS、PolyI-C、IL-1、IFN-γ、PDGF、EGF或某些病毒刺激下均可被诱导分泌MCP-1。
本发明所述的CYFRA21-1是细胞角蛋白19的可溶性片段，主要用做肿瘤标志物，对肺癌的诊断有较大意义，但出人意料的，本发明发现其对肾癌也具有一定的诊断意义。
本发明另一方面还涉及肿瘤生物标志物在诊断肾癌中的应用。
本发明还涉及一种肿瘤检测试剂盒，所述检测试剂盒包括联合检测血清中单核细胞趋化蛋白1(MCP-1)、乳酸脱氢酶、层粘蛋白和CYFRA21-1含量的试剂。在本发明的一个优选实施方式中，所述的单核细胞趋化蛋白1(MCP-1)、乳酸脱氢酶、层粘蛋白和CYFRA21-1含量为ELISA试剂。
有益效果
与现有技术相比，本发明的有益效果是：
本发明是通过综合使用四种肿瘤生物标志物，能够有效提高肾癌的检测特异性。
附图说明
图1为示出不同肾癌生物标志物及其组合的ROC曲线的图。
具体实施方式
为了进一步理解本发明，下面将结合本发明实施例，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
如无特殊说明，本发明实施例中所涉及的试剂均为市售产品，均可以通过商业渠道购买获得。
实施例1
1.1一般资料
选取北京市复兴医院2018-2019年收治并确诊的肾癌患者120例，其中男性65例，女性55例；年龄50～72岁，平均(62.03±10.68)岁；收集同期在该医院体检健康者100例作为对照组，其中男性55例，女性45例；年龄50～72岁，平均(62.36±11.98)岁。两组基本资料比较差异无统计学意义(P＞0.05)。
1.2诊断标准
患者采取影像学进行确诊，影像学检查项目包括：胸部X线片(正、侧位)、腹部超声、腹部CT、腹部MRI检查。
1.3入选标准
(1)符合肾癌相关标准；(2)年龄40～75岁；(3)首次确诊者；(4)进行本研究前未接受外科手术或者靶向治疗等相关治疗；(5)患者或患者近亲属知情，且签署知情协议书。
1.4排除标准
(1)伴有心、脑、肝等脏器严重障碍者；
(2)生存期预计少于1年者；
(3)同时有其他类型肿瘤者。
1.5指标检测
所有研究对象静脉血采集均在晨起空腹进行，约3mL，血样室温离心，血清置于-70℃下保存。单核细胞趋化蛋白1(MCP-1)、乳酸脱氢酶、层粘蛋白和CYFRA21-1均测定采取酶联免疫吸附法(ELISA)，所述的检测试剂为市售的ELISA试剂，检测均使用同一批次试剂。
1.6分析指标
比较对照组健康体检者和肾癌组患者血清中单核细胞趋化蛋白1(MCP-1)、乳酸脱氢酶、层粘蛋白和CYFRA21-1水平。
1.7统计学方法
采用SPSS 19.0软件包对数据进行统计分析，计量数据用x±s表示，用x2检验比较组间差异，P＜0.05为差异有统计学意义。
1.8统计结果
与对照组比较，肾癌组患者单核细胞趋化蛋白1(MCP-1)、乳酸脱氢酶、层粘蛋白和CYFRA21-1的比较差异有统计学意义(P＜0.01)，见表1。
表1两组血清标志物水平比较/(μg·L-1)
Figure BDA0002728919050000041
分别对于患者的血清标志物水平进行ROC回归曲线分析，结果如图1所示。单核细胞趋化蛋白1(MCP-1)、乳酸脱氢酶、层粘蛋白和CYFRA21-1的AUC分别为0.62、0.62、0.73和0.75，均有一定的预测价值，但综合四种标志物的AUC为0.84，特异性更高。
1.9效果进一步验证
收集2019年1月-2020年1月在北京市复兴医院体检健康者1000例，检测其血清单核细胞趋化蛋白1(MCP-1)、乳酸脱氢酶、层粘蛋白和CYFRA21-1水平，其中3例同时满足单核细胞趋化蛋白1(MCP-1)、乳酸脱氢酶、层粘蛋白和CYFRA21-1偏高，后经病理检查确诊，2例为肾癌早期，1例为肾癌晚期。
对于本领域技术人员而言，显然本发明不限于上述示范性实施例的细节，而且在不背离本发明的精神或基本特征的情况下，能够以其他的具体形式实现本发明。因此，无论从哪一点来看，均应将实施例看作是示范性的，而且是非限制性的，本发明的范围由所附权利要求而不是上述说明限定，因此旨在将落在权利要求的等同要件的含义和范围内的所有变化囊括在本发明内。
此外，应当理解，虽然本说明书按照实施方式加以描述，但并非每个实施方式仅包含一个独立的技术方案，说明书的这种叙述方式仅仅是为清楚起见，本领域技术人员应当将说明书作为一个整体，各实施例中的技术方案也可以经适当组合，形成本领域技术人员可以理解的其他实施方式。

Claims (1)

1.一种肿瘤检测试剂盒在制备诊断或预示肾癌的诊断试剂中的应用，所述检测试剂盒包括联合检测血清中单核细胞趋化蛋白1(MCP-1)、乳酸脱氢酶、层粘蛋白和CYFRA21-1含量的试剂，所述肾癌患者血清中单核细胞趋化蛋白1(MCP-1)、乳酸脱氢酶、层粘蛋白和CYFRA21-1含量水平相比健康体检者升高。
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