CN111879931B - 一种胰腺癌分子标记物及其应用 - Google Patents
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Abstract
本发明公开了一种胰腺癌分子标记物及其应用,其包括白细胞介素IL‑4、E钙黏蛋白、糖蛋白2α(GP‑2α)和膜联蛋白A7。本发明是通过综合使用四种肿瘤分子标记物,能够有效提高胰腺癌的检测特异性。
Description
技术领域
本发明属于医学检测领域,具体是一种胰腺癌分子标记物及其应用。
背景技术
胰腺癌是目前世界上发病率第十二、死亡率第七的癌症,胰腺癌的预后极差,每年发病人数和死亡人数接近1:1。世界卫生组织2012年统计结果显示,胰腺癌是目前世界上发病率第十二和死亡率第七的癌症,全世界每年新增胰腺癌病人33万人,每年因胰腺癌死亡的病人有33万人,胰腺癌的发病人数和死亡人数的比值接近1:1。胰腺癌包括内分泌胰腺癌和外分泌胰腺癌,大部分的胰腺癌病人属于外分泌胰腺癌,其中胰腺导管腺癌病人占胰腺癌病人的90%左右。胰腺癌进展非常快,病人预后极差,胰腺癌病人的平均生存期仅为6-9个月,一年生存率为28%,五年存活率为7%;有20%的胰腺癌病人可以进行手术切除,但是可以进行手术切除的病人中有很大一部分会发生癌症复发和转移,这部分患者的中位生存期为12-19个月,五年生存率为20%,胰腺癌有“癌中之王”之称。
胰腺癌是一种恶性程度很高,诊断和治疗都很困难的消化道恶性肿瘤,约90%为起源于腺管上皮的导管腺癌。其发病率和死亡率近年来明显上升。5年生存率<1%,是预后最差的恶性肿瘤之一。胰腺癌早期的确诊率不高,手术死亡率较高,而治愈率很低。本病发病率男性高于女性,男女之比为1.5~2:1,男性患者远较绝经前的妇女多见,绝经后妇女的发病率与男性相仿。
B超、CT、MRI、ERCP、PTCD、血管造影、腹腔镜检查、肿瘤标志物测定、癌基因分析等,对胰腺癌确定诊断和判断能否手术切除有相当大的帮助。一般情况下B超、CA19-9、CEA可作为筛选性检查,一旦怀疑胰腺癌,CT检查是必要的。病人有黄疸而且比较严重,经CT检查后不能确定诊断时,可选择ERCP和PTCD检查。及早发现及早治疗对于治愈胰腺癌十分关键,而且手术切除后的患者追踪对于术后及时干预提高患者生存率至关重要。然而,通过常规的生化检测难以即使发现胰腺癌患者,并且,单一指标的敏感性较差。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,为早期预示胰腺癌奠定基础。
发明内容
本发明的目的在于提供一种胰腺癌分子标记物及其应用,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胰腺癌分子标记物,其特征在于包括白细胞介素IL-4、E钙黏蛋白、糖蛋白2α(GP-2α)和膜联蛋白A7中的至少一种,优选为至少三种,特别优选为全部四种。
本发明另一方面还涉及上述胰腺癌分子标记物在诊断胰腺癌中的应用。
本发明另一方面还涉及联合检测白细胞介素IL-4、E钙黏蛋白、糖蛋白2α(GP-2α)和膜联蛋白A7的试剂在制备诊断或预示胰腺癌的试剂盒中的应用。
在本发明的一个优选实施方式中,所述试剂盒为ELISA试剂盒。
在本发明的一个优选实施方式中,所述的试剂盒为检测血清中所述分子标记物的试剂盒。
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分子标记物,能够有效提高胰腺癌的检测特异性。
附图说明
图1为示出不同胰腺癌分子标记物及其组合的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
选取温州市中心医院2017-2019年收治并确诊的胰腺癌患者100例,其中男性65例,女性35例;年龄50~72岁,平均(65.02±9.38)岁;收集同期在温州市中心医院体检健康者100例作为对照组,其中男性60例,女性40例;年龄50~72岁,平均(64.38±8.98)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CT加ERCP和PTCD病理检查进行确诊。
1.3入选标准
(1)符合胰腺癌相关标准;(2)年龄40~75岁;(3)首次确诊者;(4)进行本研究前未接受放化疗等相关治疗;(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。白细胞介素IL-4、E钙黏蛋白、糖蛋白2α(GP-2α)和膜联蛋白A7均测定采取酶联免疫吸附法(ELISA),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胰腺癌组患者血清中白细胞介素IL-4、E钙黏蛋白、糖蛋白2α(GP-2α)和膜联蛋白A7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,胰腺癌组患者白细胞介素IL-4、E钙黏蛋白、糖蛋白2α和膜联蛋白A7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)
组别 | 例数 | 白细胞介素IL-4 | E钙黏蛋白 | 糖蛋白2α | 膜联蛋白A7 |
对照组 | 100 | 0.83±0.25 | 15.25±2.87 | 2.85±1.23 | 10.38±1.26 |
胰腺癌组 | 100 | 1.38±0.20 | 4.38±0.59 | 3.68±1.58 | 20.08±2.68 |
P值 | <0.001 | <0.001 | <0.005 | <0.001 |
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。白细胞介素IL-4、糖蛋白2α、膜联蛋白A7和E钙黏蛋白的AUC分别为0.72、0.66、0.81和0.85,均有一定的预测价值,但综合四种标志物的AUC为0.98,特异性更高。
1.9效果进一步验证
收集2019年6月-2020年2月在温州市中心医院体检健康者3000例,检测其血清白细胞介素IL-4、糖蛋白2α、膜联蛋白A7和E钙黏蛋白水平,其中2例同时满足白细胞介素IL-4、糖蛋白2α和膜联蛋白A7偏高以及E钙黏蛋白偏低,后经CT加ERCP和PTCD病理检查确诊,两例均为胰腺癌早期。
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.联合检测白细胞介素-4、E钙黏蛋白、糖蛋白2α和膜联蛋白A7的试剂在制备诊断或预示胰腺癌的试剂盒中的应用,其特征在于,所述试剂盒为ELISA试剂盒,样本来源自血清,检测时检测样本中的白细胞介素-4、E钙黏蛋白、糖蛋白2α和膜联蛋白A7。
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