CN116411080A - 一种区分冷、热肿瘤的标志物 - Google Patents
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Abstract
本发明公开了一种区分冷、热肿瘤的标志物,所述标志物包括WNT7A、PYCR3、CCL5和/或THEM4。本发明提供了检测所述生物标志物表达水平的试剂在制备区分冷热肿瘤的产品中的应用以及一种区分冷热肿瘤的试剂盒。本发明提供的生物标志物能够准确地区分冷热肿瘤,筛选对ICI治疗获益的患者,实现患者的个性化治疗。
Description
技术领域
本发明属于生物医药领域,具体涉及一种区分冷、热肿瘤的标志物。
背景技术
免疫检査点抑制剂(immune checkpoint inhibitors,ICIs)是肿瘤免疫治疗的重要组成部分之一,可以阻断T细胞负性共刺激信号通路,恢复机体的抗肿瘤免疫应答,促进T细胞对肿瘤细胞的清除。2010年,美国食品药品监督管理局(Food and drugadministration,FDA)批准首个ICI——伊匹木单抗,用于治疗黑色素瘤。ICIs的原理是解除肿瘤细胞或者TME中对T细胞活化的抑制,让免疫细胞重新识别与杀伤肿瘤细胞,对于肿瘤临床治疗具有深远的影响和意义。目前,ICIs主要包括CTLA-4抑制剂、PD-1抑制剂和PD-L1抑制剂。ICIs的优势明显:第一,持久性,对ICIs有效的病人,疗效维持的平均时间相对较长,部分患者可维持5-10年。第二,广谱性,适用于绝大多数肿瘤;第三,低毒性,相比于传统的放疗和化疗而言,ICIs的毒副作用较轻。但是,免疫治疗在肿瘤中(除了霍奇金淋巴瘤)的有效率仅20-40%,难以满足临床应用的需要。
对ICIs敏感的肿瘤具有较高水平的免疫细胞浸润,代表了一种T细胞炎性的表型,通常被称为热肿瘤;与之相反的则是对ICIs治疗不响应的低免疫浸润型肿瘤,表现为T细胞缺乏或者T细胞排斥,通常被称为冷肿瘤。
筛选能够区分冷、热肿瘤的生物标志物,筛选优势人群,进一步提高ICIs疗效,实现个性化治疗是目前所面临的挑战。
发明内容
为弥补现有技术的不足,本发明提供了区分冷热肿瘤的生物标志物。
为实现上述目的,本发明采用如下技术方案:
本发明的第一方面提供了一种生物标志物,所述生物标志物包括WNT7A、PYCR3、CCL5和/或THEM4。
本发明的第二方面提供了检测本发明第一方面所述的生物标志物表达水平的试剂在制备区分冷热肿瘤的产品中的应用。
进一步,所述试剂包括用于检测所述生物标志物mRNA或蛋白质表达水平的试剂。
进一步,检测所述生物标志物mRNA表达水平的试剂包括特异性结合所述生物标志物的引物或探针。
进一步,检测所述生物标志物蛋白表达水平的试剂包括针对所述生物标志物的蛋白质特异性抗体。
进一步,所述抗体包括单克隆抗体、重组抗体、单链抗体、嵌合抗体及其与所述生物标志物具有免疫反应性的片段。
进一步,所述试剂还包括标签。
进一步,所述标签包括放射性标签、荧光标签、化学发光标签、亲和标签或酶标签。
进一步,所述产品包括试剂盒、试纸、芯片、核酸膜条。
进一步,所述试剂盒包括通过RT-PCR法、qRT-PCR法、生物芯片检测法、DNA印迹法、原位杂交法、蛋白免疫印迹法、免疫扩散法、ELISA、免疫沉淀法、免疫组化法、空间转录组技术检测所述生物标志物基因或蛋白表达水平所需的试剂。
进一步,所述肿瘤包括子宫内膜癌、肺癌、结直肠癌、胃癌、黑色素瘤、肾癌。
进一步,所述肿瘤选自子宫内膜癌。
本发明的第三方面提供了一种区分冷热肿瘤的产品,所述产品包括检测本发明第一方面所述的生物标志物表达水平的试剂。
进一步,所述产品包括试剂盒、试纸、芯片、核酸膜条。
进一步,所述试剂盒还包括缓冲剂。
进一步,所述试剂盒还包括标签或说明书。
进一步,所述试剂盒还包括对照品。
进一步,所述肿瘤包括子宫内膜癌、肺癌、结直肠癌、胃癌、黑色素瘤、肾癌。
进一步,所述肿瘤选自子宫内膜癌。
本发明的第四方面提供了本发明第一方面所述的生物标志物在构建区分冷热肿瘤的计算模型中的应用。
进一步,所述肿瘤包括子宫内膜癌、肺癌、结直肠癌、胃癌、黑色素瘤、肾癌。
进一步,所述肿瘤选自子宫内膜癌。
本发明的第五方面提供了一种区分冷热肿瘤的系统,所述系统包括:
(1)检测单元:所述检测单元用于检测本发明第一方面所述的生物标志物的表达量;
(2)结果判断单元:所述结果判断单元用于根据检测单元所检测得到的表达量的结果,输出冷热肿瘤的判断结果;
进一步,所述结果判断单元包括输入单元、分析单元和输出单元。
进一步,所述输入单元用于输入所述生物标志物的表达量。
进一步,所述分析单元用于根据所述生物标志物的表达量,分析冷热肿瘤的类型。
进一步,所述输出单元用于输出分析单元的分析结果。
进一步,所述生物标志物表达量包括mRNA表达量、蛋白表达量。
本发明的第六方面提供了一种计算机可读存储介质,其上存储有计算机程序,所述计算机程序被处理器执行时实现本发明第五方面所述的系统。
进一步,所述肿瘤包括子宫内膜癌、肺癌、结直肠癌、胃癌、黑色素瘤、肾癌。
进一步,所述肿瘤选自子宫内膜癌。
本发明的第七方面提供了本发明第一方面所述的生物标志物在构建区分冷热肿瘤的系统中的应用。
进一步,所述肿瘤包括子宫内膜癌、肺癌、结直肠癌、胃癌、黑色素瘤、肾癌。
进一步,所述肿瘤选自子宫内膜癌。
本发明的优点和有益效果:
本发明通过空间转录组技术筛选了能够区分冷、热肿瘤的生物标志物,并采用大样本进行验证,结果证明,本发明筛选的生物标志物能够很好的区分冷、热肿瘤,具有较高的诊断效能,有助于实现子宫内膜癌患者的个性化治疗。
附图说明
图1是4基因区分冷热肿瘤箱式图,其中,1A是训练集中4基因区分冷热肿瘤箱式图,1B是验证集中4基因区分冷热肿瘤箱式图;
图2是验证集中4基因区分冷热肿瘤ROC曲线图。
具体实施方式
下文提供了本说明书中使用的一些术语的定义。除非另有说明,本文中使用的所有技术和科学用语通常具有和本发明所属领域的普通技术人员通常理解的意思相同的意思。
本发明提供了一种用于区分冷热肿瘤的生物标志物,所述生物标志物包括WNT7A、PYCR3、CCL5和/或THEM4。
在本发明中,WNT7A包括野生型、突变型或其片段。该术语涵盖全长,未加工的WNT7A,源自细胞中加工的任何形式的WNT7A,以及WNT7A的天然发生变体(例如剪接变体或等位变体)。该术语涵盖例如人的WNT7A以及来自任何其它脊椎动物来源,包括哺乳动物,诸如灵长动物和啮齿动物(例如小鼠和大鼠)的WNT7A,基因ID:7476。
PYCR3包括野生型、突变型或其片段。该术语涵盖全长,未加工的PYCR3,源自细胞中加工的任何形式的PYCR3,以及PYCR3的天然发生变体(例如剪接变体或等位变体)。该术语涵盖例如人的PYCR3以及来自任何其它脊椎动物来源,包括哺乳动物,诸如灵长动物和啮齿动物(例如小鼠和大鼠)的PYCR3,基因ID:65263。
CCL5包括野生型、突变型或其片段。该术语涵盖全长,未加工的CCL5,源自细胞中加工的任何形式的CCL5,以及CCL5的天然发生变体(例如剪接变体或等位变体)。该术语涵盖例如人的CCL5以及来自任何其它脊椎动物来源,包括哺乳动物,诸如灵长动物和啮齿动物(例如小鼠和大鼠)的CCL5,基因ID:6352。
THEM4包括野生型、突变型或其片段。该术语涵盖全长,未加工的THEM4,源自细胞中加工的任何形式的THEM4,以及THEM4的天然发生变体(例如剪接变体或等位变体)。该术语涵盖例如人的THEM4以及来自任何其它脊椎动物来源,包括哺乳动物,诸如灵长动物和啮齿动物(例如小鼠和大鼠)的THEM4,基因ID:117145。
在本发明中,生物标志物指具有特异性生物学特性、生物化学特征的分子指示物,其可用于确定存在或不存在特定疾病或状况和/或特定疾病或状况的严重程度。
在本发明中,和/或在两个或更多个项目的列表中使用时,意指所列项目中的任何一个可单独使用,也可与所列项目中的任何一个或多个结合使用。例如,表达A和/或B旨在意指A和B中的任一个或两个,即,单独A,单独B,或者A和B组合。表达A、B和/或C旨在意指单独A、单独B、单独C、A和B组合、A和C组合、B和C组合或A、B和C组合。
所述试剂包括用于检测所述生物标志物mRNA或蛋白质表达水平的试剂。
检测所述生物标志物mRNA表达水平的试剂包括特异性结合所述生物标志物的引物或探针。
在本发明中,检测mRNA表达水平的方法包括但不限于RT-PCR、qRT-PCR法、RNA酶保护测定法(RPA;RNaseprotectionassay)、DNA微阵列芯片、生物芯片检测法、DNA印迹法、原位杂交法。
在本发明中,表达水平或表达量一般指生物学样品中生物标志物的量。表达一般指信息(例如基因编码和/或表观遗传信息)转化成细胞中存在并运行的结构的过程。因此,如本发明中使用的,表达可以指转录成多核苷酸,翻译成多肽,或甚至多核苷酸和/或多肽修饰(例如多肽的翻译后修饰)。转录的多核苷酸的,翻译的多肽的,或多核苷酸和/或多肽修饰(例如多肽的翻译后修饰)的片段也应视为表达的,无论它们是源自通过可变剪接生成的转录物或经过降解的转录物,或者是源自多肽的翻译后加工(例如通过蛋白水解)。
在本发明中,引物(primer)是指作为DNA合成的起点(starting point)的短单链寡核苷酸(short single strand oligonucleotide)。引物在合适的缓冲液(buffer)和温度条件下与模板(template)多核苷酸特异结合,并且通过DNA聚合酶在引物中添加并结合具有模板DNA互补碱基的三磷酸核苷以合成DNA。引物通常由15-30个碱基序列组成,与模板链结合的熔化温度(melting temperature,Tm)随碱基的构成和长度而不同。
引物序列不需具备与模板的部分碱基序列完全互补的序列,只要具有能与模板杂交并发挥引物固有作用范围内的充分的互补性即可。因此,本发明中用于测定所述生物标志物的表达水平的引物不需具备与各基因序列完全互补的序列,只要具有能通过DNA合成达到扩增mRNA或cDNA的特定区域来测定mRNA的量这一目的的长度和互补性即可。用于所述扩增反应的引物由分别与待扩增mRNA的特定区域两个末端的模板(或正义,sense)链和相反(反义,antisense)链互补结合的一组(对)链组成。
探针可为单链或双链。探针的准确长度取决于多种因素,包括温度、探针来源和使用方法。例如,对于诊断应用,根据靶序列的复杂性,寡核苷酸探针通常包含15-25个或更多个核苷酸,尽管其可包含更少的核苷酸。在某些实施方案中,探针可为5-100个连续碱基,并且通常为约5、10、12、13、14、15、16、17、18、19、20、21、22、23、24或25个核苷酸长度,或者可为约30、35、40、45、50、55、60、65、70、75、80、85、90、95或100个核苷酸长度。为了达到本发明的目的,与WNT7A、PYCR3、CCL5和/或THEM4的mRNA互补的探针可通过与被检体样本进行杂交反应(hybridization)来测量WNT7A、PYCR3、CCL5和/或THEM4的表达水平,用于区分冷热肿瘤。探针的选择和杂交条件可以根据本领域已知的技术适当地进行选择。
本发明的引物或探针可以使用亚磷酰胺(phosphoramidite)固相合成法或其他公知的方法化学性合成。引物或探针只要在不干扰与WNT7A、PYCR3、CCL5和/或THEM4的mRNA的杂交的范围内,可以用本领域已知的方法对其进行各种转换。这类转换如甲基化、封端、用一种或多种天然核苷酸类似物取代以及核苷酸之间的转换,如使用不带电荷的接头(例如:甲基膦酸酯、磷酸三酯、氨基磷酸酯和氨基甲酸酯)或带电荷的接头(例如:硫代磷酸酯、硫代磷酸酯)。
检测所述生物标志物蛋白表达水平的试剂包括针对所述生物标志物的蛋白质特异性抗体。
在本发明中,检测蛋白表达水平的方法包括但不限于蛋白免疫印迹法、ELISA(酶联免疫吸附测定)、免疫扩散法(放射性免疫扩散法(Radioimmunodiffusion)、奥克特洛尼(Ouchterlony)免疫扩散法)、火箭(Rocket)电泳法、免疫组化法(免疫组织化学技术)、免疫沉淀法(immunoprecipitationassay)、补体结合测定法(completefixationassay)、FACS、蛋白质芯片(proteinchip)。
在本发明中,抗体(antibody)是指特异性结合于抗原位点的免疫球蛋白(immunoglobulin)。本发明的抗体不与WNT7A、PYCR3、CCL5和/或THEM4以外的其他种类的蛋白质发生反应,是只与WNT7A、PYCR3、CCL5和/或THEM4蛋白质特异结合的抗体。WNT7A、PYCR3、CCL5和/或THEM4抗体可以通过将每个基因克隆到表达载体中以获得由所述基因编码的蛋白质,然后可使用本领域的常规方法从所获得的蛋白质进行制备。使用包含WNT7A、PYCR3、CCL5和/或THEM4抗原位点的WNT7A、PYCR3、CCL5和/或THEM4蛋白质片段可以制备各所述蛋白质特异抗体。本发明的抗体包括单克隆抗体、重组抗体、单链抗体、嵌合抗体及其与所述生物标志物具有免疫反应性的片段。此外,只要具有抗原-抗体结合性,即使是完整抗体的一部分也包括在本发明的抗体中,同时包括与WNT7A、PYCR3、CCL5和/或THEM4特异结合的所有种类的免疫球蛋白抗体。例如,不仅包括具有两条全长轻链和两条全长重链的完整形式的抗体,而且包括具有抗原结合功能的Fab、F(ab’)、F(ab’)2和Fv等。
在本发明中,特异性结合是指其中两种或更多种分子形成可在生理或测定条件下测量的复合物并为选择性的情况。将抗体或抗原结合蛋白或其他分子在以下情况下称为特异性结合到蛋白、抗原或表位:在适当选择的条件下,这种结合不受到实质性抑制,而同时非特异性结合受到抑制。特异性结合的特征在于高亲和力以及对化合物、蛋白、表位或抗原的选择性。非特异性结合通常具有较低的亲和力。
所述试剂还包括标签。
所述标签包括放射性标签、荧光标签、化学发光标签、亲和标签或酶标签。
在本发明中,标签是指可提供可检测信号的物质。
其中,放射性标签包括但不限于3H、14C、35S、125I、131I。
荧光标签包括但不限于藻红蛋白(PE)或吲哚菁(Cy5)。
化学发光标签包括但不限于草酰氯(oxalyl chloride)、罗丹明6G、Ru(bipy)32、四(二甲氨基)乙烯(TMAE,tetrakis(dimethylami no)ethylene)、邻苯三酚(1,2,3-三羟基苯)(Pyrogallol(1,2,3-trihydroxibenzene))、光泽精(Lucigenin)、过氧草酸盐(peroxyoxalates)、芳基草酸盐(Aryloxalates)、吖啶酯(Acridinium esters)、二氧杂环丁烷(dioxetanes)及其他物质。
亲和标签包括但不限于生物素、His-tag、Flag-tag、strep-tag、糖、脂质、甾醇、PEG-连接子和辅助因子。
酶标签包括但不限于辣根过氧化物酶(HRP)、β-半乳糖苷酶、荧光素酶、碱性磷酸酶、乙酰胆碱酶。
所述产品包括试剂盒、试纸、芯片、核酸膜条。
在本发明中,试剂盒还包括缓冲剂、防腐剂或蛋白质稳定剂。试剂盒也可包含用于检测可检测试剂的必要成分(例如底物)。试剂盒也可含有对照样品或一系列对照样品,其可被测定并与所含有的试验样品进行比较。
试剂盒的其它成分包括但不限于:用于采集生物样品的工具、用于标记检测试剂(结合剂)的工具、用于固定生物样品中所述生物标志物蛋白或所述生物标志物核酸的膜、用于将生物样品加样到膜上的工具、用于使试剂与受试者生物样品中的生物标志物结合的工具、第二抗体、用于从受试者生物液体中分离总RNA的工具、用于进行凝胶电泳的工具、用于从分离的总RNA产生cDNA的工具、用于进行杂交测定的工具,以及用于进行PCR的工具。
试剂盒可任选包括有关试剂盒成分和/或如何进行各种测定(例如所述生物标志物水平、与对照标准品的比较等)的信息的一组印刷形式或电子形式(例如磁盘或光盘)的标签或说明书。
试剂盒的组分可以以水介质的形式或以冻干的形式来包装。试剂盒中适当的容器通常至少包括一种小瓶、试管、长颈瓶、宝特瓶、针筒或其它容器,其中可放置一种组分,并且优选地,可进行适当地等分。在试剂盒中存在多于一种的组分时,试剂盒中通常也将包含第二、第三或其它附加的容器,其中分离地放置附加的组分。然而,不同组合的组分可被包含在一个小瓶中。本发明的试剂盒通常也将包括一种用于容纳反应物的容器,密封以用于商业销售。这种容器可包括注模或吹模的塑料容器,其中可保留所需的小瓶。
在本发明中,芯片也称为阵列,指包含连接的核酸或肽探针的固体支持物。阵列通常包含按照不同的已知位置连接至基底表面的多种不同的核酸或肽探针。这些阵列也称为微阵列,通常可以利用机械合成方法或光引导合成方法来产生这些阵列,所述光引导合成方法合并了光刻方法和固相合成方法的组合。阵列可以包含平坦的表面,或者可以是珠子、凝胶、聚合物表面、诸如光纤的纤维、玻璃或任何其它合适的基底上的核酸或肽。可以以一定的方式来包装阵列,从而允许进行全功能装置的诊断或其它方式的操纵。
在本发明中,核酸膜条包括基底和固定于所述基底上的寡核苷酸探针;所述基底可以是任何适于固定寡核苷酸探针的基底,例如尼龙膜、硝酸纤维素膜、聚丙烯膜、玻璃片、硅胶晶片、微缩磁珠。
在本发明中,肿瘤是指由细胞过度生长或增殖引起的任何组织块,包括良性(非癌性)或恶性(癌性),包括癌前病变。
本发明的肿瘤包括但不限于肾上腺皮质癌、肛门癌、阑尾癌、星形细胞瘤(小脑星形细胞瘤、大脑星形细胞瘤、儿童大脑星形细胞瘤、松果体星形细胞瘤)、基底细胞癌、胆管癌、膀胱癌、骨肿瘤、脑癌、乳腺癌、支气管腺瘤、类癌瘤、原发性不明的癌、宫颈癌、慢性骨髓增生性紊乱、促结缔组织增生性小圆细胞肿瘤、子宫内膜癌、室管膜瘤、上皮样血管内皮瘤(EHE)、食管癌、尤因肿瘤肉瘤家族、颅外生殖细胞肿瘤、性腺外生殖细胞肿瘤、眼癌、胆囊癌、妊娠性滋养层细胞瘤、胶质瘤、结直肠癌、头颈癌、心脏癌、肝癌、胰岛细胞癌、卡波西肉瘤、肾癌(肾细胞癌)、喉癌、白血病、唇癌、脂肪肉瘤、肺癌(非小细胞肺癌、小细胞肺癌)、淋巴瘤(非霍奇金淋巴瘤、霍奇金淋巴瘤、艾滋病相关淋巴瘤、伯基特淋巴瘤、皮肤T细胞淋巴瘤)、巨球蛋白血症、骨恶性纤维组织细胞瘤/骨肉瘤、髓母细胞瘤、黑素瘤、梅克尔细胞癌、多发性内分泌肿瘤综合征、骨髓癌、蕈样肉芽肿瘤、骨髓增生异常综合征、粘液瘤、鼻腔和副鼻窦癌、神经母细胞瘤、卵巢癌、胰腺癌、阴茎癌、咽癌(下咽癌、鼻咽癌、口咽癌、嗜铬细胞瘤、松果体母细胞瘤、幕上原始神经外胚层肿瘤、垂体腺瘤、胸膜肺母细胞瘤、前列腺癌、肾盂和输尿管移行细胞癌、视网膜母细胞瘤、横纹肌肉瘤、唾液腺癌、Sézary综合征、软组织肉瘤、鳞状细胞癌、胃癌、睾丸癌、胸腺瘤、甲状腺癌、尿道癌、阴道癌。
在本发明的具体实施方案中,肿瘤选自子宫内膜癌。
下面结合具体实施例进一步阐述此发明。应理解的是,在此描述的特定实施方式通过举例的方式来表示,并不作为对本发明的限制。在不偏离本发明范围的情况下,本发明的主要特征可以用于各种实施方式。
实施例
1实验材料
85例子宫内膜癌样本制成的组织芯片(每个TMA为2毫米直径):2019年到2021年在四川省人民医院被诊断为子宫内膜癌的病理组织样本。
2实验方法
2.1子宫内膜癌组织芯片的处理
采用Nanostring的RNA杂交探针(检测包括免疫应答,肿瘤微环境,肿瘤生物学、肿瘤炎症相关的近2000种mRNA的表达)与TMA病理切片过夜孵育,从而与样本中的目标RNA原位杂交(RNA杂交探针除了包含于目标RNA结合的部位,还带有可以紫外光解的linker基团,用以与带有特定标签的DNA序列的连接)。杂交之后,用多色荧光抗体对样本进行形态学标记,并进行扫描成像,从而区分肿瘤细胞、间质或免疫区域。之后,针对TMA切片中的每一例样本选定肿瘤中心、侵袭边缘和间质免疫细胞区域,再分别进行紫外照射。此时探针上可光解的linker断裂,其连接的DNA序列被释放,并被毛细管吸收至96孔板中。这些收集到的DNA序列由几个部分所组成:RNA靶标特异性的标记、特异性分子标签UMI以及引物结合位点。因此可用于RNA的识别、二代测序(next generation sequencing,NGS)以及样本的区分(sample demultiplexing)。随后对DNA序列进行建库,纯化PCR产物,再进行测序。NGS的数据信息随后被追溯到TMA病理切片上选定的具体位置,从而实现对每一个样本的每个选定区域进行原位靶标丰度的分析。
2.2免疫组化
对每一例肿瘤病理样本进行连续切片,随后在60℃下孵育1小时。经过二甲苯脱蜡,梯度酒精复水,抗原修复后,用3%H2O2进行封闭,然后对MLH1(克隆ES05)、MSH2(克隆RED2)、MSH6(克隆EP49)、PMS2(克隆EP51)、CD8(克隆SP16)进行染色。一抗4℃过夜孵育后,用二抗孵育30分钟,随后进行DAB显色(Dako REALTMEnVisionTM)。最后玻片用苏木素染色并封片。
2.3免疫组化判读标准
CD8+T细胞密度:CD8+TILs的密度以浸润到肿瘤细胞区域的CD8+T细胞的数量来评价。对于每个样本,从五个随机选择的高倍视野中对CD8+T细胞计数,再取平均值作为该样本的CD8+T细胞密度。
2.4统计分析
WGCNA和Lasso回归分析筛选和肿瘤区域CD8+T细胞浸润相关的核心基因表达谱标志物。
2.5冷热肿瘤判断标准
针对85例子宫内膜癌样本,通过CD8免疫组化实验计算每个样本的CD8+T细胞的密度,然后取中位数。CD8+T细胞密度大于或等于中位数的定义为热肿瘤,小于中位数的定义为冷肿瘤。
2.6 ROC曲线
将85例子宫内膜癌样本分为训练集(30例)和验证集(55例),并制作ROC曲线分析诊断效能。
3实验结果
相对于冷肿瘤,筛选得到的WNT7A、PYCR3、CCL5和THEM4基因在热肿瘤中显著高表达(图1),且具有较高的诊断效能,AUC达到了0.871(图2)。
上述实施例的说明只是用于理解本发明的方法及其核心思想。应当指出,对于本领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以对本发明进行若干改进和修饰,这些改进和修饰也将落入本发明权利要求的保护范围内。
Claims (10)
1.一种生物标志物,其特征在于,所述生物标志物包括WNT7A、PYCR3、CCL5和/或THEM4。
2.检测权利要求1所述的生物标志物表达水平的试剂在制备区分冷热肿瘤的产品中的应用;
优选的,所述试剂包括用于检测所述生物标志物mRNA或蛋白质表达水平的试剂;
优选的,检测所述生物标志物mRNA表达水平的试剂包括特异性结合所述生物标志物的引物或探针;
优选的,检测所述生物标志物蛋白表达水平的试剂包括针对所述生物标志物的蛋白质特异性抗体;
优选的,所述抗体包括单克隆抗体、重组抗体、单链抗体、嵌合抗体及其与所述生物标志物具有免疫反应性的片段。
3.根据权利要求2所述的应用,其特征在于,所述试剂还包括标签;
优选的,所述标签包括放射性标签、荧光标签、化学发光标签、亲和标签或酶标签。
4.根据权利要求2所述的应用,其特征在于,所述产品包括试剂盒、试纸、芯片、核酸膜条;
优选的,所述试剂盒包括通过RT-PCR法、qRT-PCR法、生物芯片检测法、DNA印迹法、原位杂交法、蛋白免疫印迹法、免疫扩散法、ELISA、免疫沉淀法、免疫组化法、空间转录组技术检测所述生物标志物基因或蛋白表达水平所需的试剂。
5.根据权利要求2所述的应用,其特征在于,所述肿瘤包括子宫内膜癌、肺癌、结直肠癌、胃癌、黑色素瘤、肾癌;
优选的,所述肿瘤选自子宫内膜癌。
6.一种区分冷热肿瘤的产品,其特征在于,所述产品包括检测权利要求1所述的生物标志物表达水平的试剂;
优选的,所述产品包括试剂盒、试纸、芯片、核酸膜条;
优选的,所述试剂盒还包括缓冲剂;
优选的,所述试剂盒还包括标签或说明书;
优选的,所述试剂盒还包括对照品。
7.权利要求1所述的生物标志物在构建区分冷热肿瘤的计算模型中的应用。
8.一种区分冷热肿瘤的系统,其特征在于,所述系统包括:
(1)检测单元:所述检测单元用于检测权利要求1所述的生物标志物的表达量;
(2)结果判断单元:所述结果判断单元用于根据检测单元所检测得到的表达量的结果,输出冷热肿瘤的判断结果;
优选的,所述结果判断单元包括输入单元、分析单元和输出单元;
优选的,所述输入单元用于输入所述生物标志物的表达量;
优选的,所述分析单元用于根据所述生物标志物的表达量,分析冷热肿瘤的类型;
优选的,所述输出单元用于输出分析单元的分析结果;
优选的,所述生物标志物表达量包括mRNA表达量、蛋白表达量。
9.一种计算机可读存储介质,其特征在于,其上存储有计算机程序,所述计算机程序被处理器执行时实现权利要求8所述的系统。
10.权利要求1所述的生物标志物在构建区分冷热肿瘤的系统中的应用。
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2021091747A1 (en) * | 2019-11-04 | 2021-05-14 | Merck Sharp & Dohme Corp. | ANGIOGENESIS AND mMDSC GENE EXPRESSION BASED BIOMARKER OF TUMOR RESPONSE TO PD-1 ANTAGONISTS |
CN113969312A (zh) * | 2021-11-28 | 2022-01-25 | 青岛泱深生物医药有限公司 | 用于预测溃疡性结肠炎患者对戈利木单抗药物敏感性的标志物 |
EP4130297A1 (en) * | 2021-08-05 | 2023-02-08 | Beijing OriginPoly Bio-Tec Co., Ltd. | Markers, primers, probes and kit for early screening and diagnosis of endometrial cancer |
-
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- 2023-03-28 CN CN202310314160.2A patent/CN116411080B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2021091747A1 (en) * | 2019-11-04 | 2021-05-14 | Merck Sharp & Dohme Corp. | ANGIOGENESIS AND mMDSC GENE EXPRESSION BASED BIOMARKER OF TUMOR RESPONSE TO PD-1 ANTAGONISTS |
EP4130297A1 (en) * | 2021-08-05 | 2023-02-08 | Beijing OriginPoly Bio-Tec Co., Ltd. | Markers, primers, probes and kit for early screening and diagnosis of endometrial cancer |
CN113969312A (zh) * | 2021-11-28 | 2022-01-25 | 青岛泱深生物医药有限公司 | 用于预测溃疡性结肠炎患者对戈利木单抗药物敏感性的标志物 |
Non-Patent Citations (3)
Title |
---|
BETTINA SOBOTTKA等: "Establishing standardized immune phenotyping of metastatic melanoma by digital pathology", LAB INVEST, vol. 101, no. 12, pages 1561 - 1570, XP037618662, DOI: 10.1038/s41374-021-00653-y * |
YONGCHAO DOU等: "Proteogenomic Characterization of Endometrial Carcinoma", CELL, vol. 180, no. 4, pages 1 * |
YU MA等: "Immunophenotyping of pulmonary sarcomatoid carcinoma", FRONT IMMUNOL, vol. 13, pages 976739 - 976752 * |
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