CN110988346A - 一种辅助诊断肺癌的标记物以及检测方法 - Google Patents
一种辅助诊断肺癌的标记物以及检测方法 Download PDFInfo
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Abstract
本发明涉及医学领域,尤其涉及一种辅助诊断肺癌的标记物以及检测方法。具体地,本发明提供了层粘连蛋白5在制备检测肺癌的诊断试剂或试剂盒中的用途。研究表明,层粘连蛋白5在肺癌组织中的表达量高于其癌旁正常组织,且层粘连蛋白5在肺癌患者血液中的含量显著高于正常人群。因此,层粘连蛋白5可作为肺癌的诊断的标志物。发明人首次发现了层粘连蛋白5可用作肺癌标志物,可用作科研或医疗等领域,具有广泛的应用价值。
Description
技术领域
本发明涉及医学领域,尤其涉及一种辅助诊断肺癌的标记物以及检测方法。
背景技术
肺癌的死亡率在全球范围内都是最高的,其中一个主要的原因是肺癌的早期诊断不具备成熟手段,当肿瘤被发现时,大多处于中晚期阶段。再加上肺癌肿瘤的病变速度极快,使得肺癌的早期诊断成为肺癌诊疗和延缓患者生命的关键。
癌症的早期诊断是一个国际性难题。然而疾病的早期诊断对于疾病的治疗和预防起到了至关重要的作用。比如癌症的早期诊断可以更有效清除组织中的肿瘤细胞从而可以成倍的提高患者的存活率。可是早期癌症阶段的肿瘤细胞尺寸较小,难以用成像诊断发现,从而加大了癌症早期诊断的难度。另一方面,因为没有有效的诊疗手段,有时良性肿瘤被误诊为癌细胞,又给患者带来不必要的经济和精神负担这就是为什么人类需要用于疾病早期诊断的蛋白质生物标记物。蛋白质决定了细胞的生物功能,也是进行诊断检查和治疗的基础,虽然我们身体蛋白质合成是由基因编码决定的,但是调节和控制分子网络和细胞生理途径的却是蛋白质及其修饰。蛋白质通过整合我们的基因和环境的信息,并随着时间动态、实时地揭示着我们的生理健康和疾病的状态。如果我们想要理解基本的生物过程、确定疾病的分子生物学基础、确定新的药物靶标并发现和验证新的诊断试验,那么蛋白质的定量测定是必不可少的。同时诊断试验如果能在早期检测出疾病,将很大程度上提高患者的生存几率。换句话说,蛋白质的定量检测对个性化医疗的发展是必不可少的,这不仅能降低医疗成本,同时还提高了治疗效果。但是现有的肺癌蛋白质标志物存在敏感性低或特异性低等问题。因此,本领域亟需开发可用于检测或判断肺癌的特异标志物。
发明内容
本发明的目的在于提供一种可用于检测或判断肺癌的特异标志物及其用途。
本发明第一个方面公开了一种层粘连蛋白5或其特异性抗体的用途,其可用于制备检测肺癌的诊断试剂或试剂盒。
术语“层粘连蛋白-5”是基底膜的主要组成蛋白之一,对上皮细胞与基底膜之间的稳定结合起着重要的作用。
优选的,其用于制备血液检测肺癌的诊断试剂或试剂盒。
术语“诊断试剂”是指采用免疫学、微生物学、分子生物学等原理或方法制备的、在体外用于对人类疾病的诊断、检测及流行病学调查等的诊断试剂。诊断试剂从一般用途来分,可分为体内诊断试剂和体外诊断试剂两大类。
术语“诊断试剂盒”是指能对人体体液、血液等反映人体健康状况的物质作出定性、定量的检测。
优选的,所述层粘连蛋白5或其特异性抗体偶联有或带有可检测标记。
在本发明的一些实施例中,所述的试剂包括抗体、引物、探针、核酸芯片或蛋白质芯片。
术语“引物”意指一小段单链DNA或RNA,作为DNA复制的起始点,除非特定限制,否则所述术语涵盖自然中生物的DNA复制和聚合酶链式反应(PCR)中人工合成的引物(通常为DNA引物)。之所以需要引物是因为在DNA合成中DNA聚合酶仅仅可以把新的核苷酸加到已有的DNA链上。除非特定限制,否则上游引物为在DNA复制时,作为DNA模板3’端的复制起始点的引物,下游引物为在DNA复制时,作为DNA模板5’端的复制起始点的引物。
优选的,所述试剂盒还联合检测其他肺癌标记物的表达;
其中,所述的其他肺癌标记物包括:人成纤维细胞活化蛋白、NNMT(抗尼克酰胺-N-甲基转移酶)、CD44或组合。
应当理解,本发明的其他肺癌标记物并不限于以上几种,本领域技术人员可以根据需要,选择任意合适的肺癌标记物来完成本发明的技术方案,且均在本发明的保护范围之内。
其中,烟碱N甲基转移酶(NNMT)利用S-腺苷甲硫胺酸作为甲基供体,是烟碱(维生素B3)的甲基化酶。CD44是I型跨膜糖蛋白,可通过对透明质酸(HA)的亲和力或通过胞外基质(ECM)的其他部分来介导细胞-细胞相互作用和细胞-基质相互作用。
本发明第二个方面公开了一种用于检测肺癌的诊断试剂盒,包括:
(a)层粘连蛋白5的抗体;和/或
(b)特异性扩增层粘连蛋白5mRNA或层粘连蛋白5cDNA的引物或引物对。
本发明的抗体可以通过本领域内技术人员已知的各种技术进行制备。
优选的,所述的试剂盒含有一容器,所述容器中含有层粘连蛋白5或其特异性抗体。
更优选的,所述试剂盒还包括标签或说明书。
在本发明的一些实施例中,所述的标签或说明书中注明以下内容:
如果检测对象的层粘连蛋白5mRNA的量与一般人群中层粘连蛋白5mRNA的量之比≥1.6,则该对象发生肺癌的几率大于正常人群。
在本发明的一些较佳实施例中,检测对象的层粘连蛋白5mRNA的量与一般人群中层粘连蛋白5mRNA的量之比≥1.8。
应当理解,检测对象的层粘连蛋白5mRNA的量与一般人群中层粘连蛋白5mRNA的量的比例并不限于上述比例,本领域技术人员可以根据需要,选择任意合适的比例,且均在本发明的保护范围之内。
优选的,所述试剂盒还联合检测其他肺癌标记物的表达;
其中,所述的其他肺癌标记物包括:人成纤维细胞活化蛋白、NNMT、CD44或组合。
本发明第三个方面公开了一种层粘连蛋白5或其特异性抗体的用途,它与选自下组中的一种或多种标记物或其相对应的特异性抗体联合用于制备血清检肺癌的诊断试剂或试剂盒,
a)人成纤维细胞活化蛋白;
b)NNMT;
c)CD44。
本发明第四个方面公开了一种层粘连蛋白5的mRNA、cDNA或蛋白的用途,它与选自下组中的一种或多种标记物的mRNA、cDNA或蛋白联合用于制备检测肺癌的试剂或试剂盒,
a)人成纤维细胞活化蛋白;
b)NNMT;
c)CD44。
在符合本领域常识的基础上,上述各优选条件,可任意组合,而不超出本发明的构思与保护范围。
本发明相对于现有技术具有如下的显著优点及效果:
层粘连蛋白5是本发明人首次发现的一个肺癌血清标志物,可应用于肺癌的早期诊断。提供了一种新的通过血清标志物检测和判断肺癌的方法,有助于早期检测或辅助检测肺癌,从而有助于尽早确诊并采取相应治疗措施。血清检测方法更方便快速,更容易为病人接受,还可以用于科研领域,具有广泛的应用价值。
具体实施方式
下面结合实施例对本发明的技术方案进行详细描述,但并不因此将本发明限制在所述的实施例范围之中。
下列实施例中未注明具体条件的实验方法,按照常规方法和条件,或按照商品说明书选择。本发明所用试剂和原料均市售可得。
本发明人经过深入的研究,首次意外的发现,层粘连蛋白5在肺癌组织高表达且在正常肺组织中低表达,因此可用作肺癌标志物。
实施例1
本实施例研究肺癌及癌旁组织样本中的层粘连蛋白5mRNA的表达量差异,发明人通过高通量的基因表达谱芯片筛选技术,发现层粘连蛋白5的基因在肺癌中高表达。然后对50对临床肺癌及癌旁组织样本中的层粘连蛋白5mRNA的表达量进行检测,采用定量RT-PCR实验检测结果表明,层粘连蛋白5mRNA在肺癌中表达较癌旁组织样本高1.8倍以上的有41对,其高表达比例约为80%。该实施例说明层粘连蛋白5可作为一个新的肺癌血清标志物,可应用于肺癌的早期诊断。
实施例2
本实施例研究肺癌及癌旁组织样本中的层粘连蛋白5蛋白表达水平的差异,在该实施例中,发明人进一步用免疫印迹试验检测了50对肺癌及癌旁组织样本中的层粘连蛋白5的蛋白表达水平,结果验证了层粘连蛋白5在44对样品中上调表达,其比例为88%。该实施例说明层粘连蛋白5可作为一个新的肺癌血清标志物,可应用于肺癌的早期诊断。
实施例3
本实施例公开了一种层粘连蛋白5或其特异性抗体的用途,它与选自下组中的标记物或其相对应的特异性抗体联合用于制备血清检肺癌的诊断试剂或试剂盒,
a)人成纤维细胞活化蛋白;
b)NNMT;
c)CD44。
实施例4
本实施例公开了一种层粘连蛋白5的mRNA、cDNA或蛋白的用途,它与选自下组中的标记物的mRNA、cDNA或蛋白联合用于制备检测肺癌的试剂或试剂盒,
a)人成纤维细胞活化蛋白;
b)NNMT;
c)CD44。
上述实施例为本发明较佳的实施方式,但本发明的实施方式并不受上述实施例的限制,其他的任何未背离本发明的精神实质与原理下所作的改变、修饰、替代、组合、简化,均应为等效的置换方式,都包含在本发明的保护范围之内。
Claims (10)
1.一种层粘连蛋白5或其特异性抗体的用途,其特征在于,用于制备检测肺癌的诊断试剂或试剂盒。
2.根据权利要求1所述的用途,其特性在于,所述层粘连蛋白5或其特异性抗体偶联有或带有可检测标记。
3.根据权利要求1所述的用途,其特征在于,所述试剂盒还联合检测其他肺癌标记物的表达;
其中,所述的其他肺癌标记物包括:人成纤维细胞活化蛋白、NNMT、CD44或组合。
4.一种用于检测肺癌的诊断试剂盒,其特征在于,包括:
(a)层粘连蛋白5的抗体;和/或
(b)特异性扩增层粘连蛋白5mRNA或层粘连蛋白5cDNA的引物或引物对。
5.根据权利要求4所述的试剂盒,其特征在于,所述的试剂盒含有一容器,所述容器中含有层粘连蛋白5或其特异性抗体。
6.根据权利要求5所述的试剂盒,其特征在于,所述试剂盒还包括标签或说明书。
7.根据权利要求6所述的试剂盒,其特征在于,所述的标签或说明书中注明以下内容:
如果检测对象的层粘连蛋白5mRNA的量与一般人群中层粘连蛋白5mRNA的量之比≥1.6,则该对象发生肺癌的几率大于正常人群。
8.根据权利要求4所述的试剂盒,其特征在于,所述试剂盒还联合检测其他肺癌标记物的表达;
其中,所述的其他肺癌标记物包括:人成纤维细胞活化蛋白、NNMT、CD44或组合。
9.一种层粘连蛋白5或其特异性抗体的用途,其特征在于,它与选自下组中的一种或多种标记物或其相对应的特异性抗体联合用于制备血清检肺癌的诊断试剂或试剂盒,
a)人成纤维细胞活化蛋白;
b)NNMT;
c)CD44。
10.一种层粘连蛋白5的mRNA、cDNA或蛋白的用途,其特征在于,它与选自下组中的一种或多种标记物的mRNA、cDNA或蛋白联合用于制备检测肺癌的试剂或试剂盒,
a)人成纤维细胞活化蛋白;
b)NNMT;
c)CD44。
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CN112540176B (zh) * | 2020-07-08 | 2021-09-28 | 深圳霁因生物医药转化研究院 | 用于诊断fap表达异常相关疾病的试剂盒、方法及计算机可读存储介质 |
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