CN111624342A - 一种卵巢癌的外周血tcr标志物及其检测试剂盒和应用 - Google Patents
一种卵巢癌的外周血tcr标志物及其检测试剂盒和应用 Download PDFInfo
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Abstract
本发明公开了一种卵巢癌的外周血TCR标志物及其检测试剂盒和应用，该标志物包括序列为SEQ ID NO.1～100所示蛋白中的至少一种。本发明基于高通量测序方法，只需要采取少量外周血，提取RNA，通过对样本的处理建立免疫图谱文库，再经过高通量测序和TCR数据分析，首先确定卵巢癌外周血中特征性TCR序列，然后将待测样本测试结果与该特征性TCR序列比对，从而确定是否患有卵巢癌。本发明能够同时比较巨大数量的卵巢癌特异性TCR序列，相比单独检测一种或几种标记物，具有更高的特异性和准确性，提高了诊断效率。
Description
技术领域
本发明属于基因工程技术领域，尤其涉及一种卵巢癌的外周血TCR标志物及其检测试剂盒和应用。
背景技术
据世界卫生组最新统计数据显示，卵巢癌在女性常见肿瘤中发病率位居第6位，在我国，卵巢癌年发病率居女性生殖系统肿瘤第3位，位于子宫颈癌和子宫体恶性肿瘤之后，呈逐年上升的趋势。卵巢癌是妇科肿瘤中死亡率最高的恶性肿瘤之一，其特点是早期无症状，大部分患者在做出诊断时已处于晚期，其5年生存率仅为35％左右原因：起病隐匿、早期诊断困难。目前卵巢癌的早期诊断率约为25％，75％的患者确诊时已为国际妇产科协会(FIGO)III-IV期，5年生存率不足50％。且初治治疗后有70％的病友会在三年内复发。卵巢上皮癌在实施病灶切除术时肿瘤局限于卵巢的概率不足30％，大多数患者的癌细胞已经扩散到盆腔与腹腔器官，故而早期诊断在卵巢癌治疗中十分重要，可大大降低死亡率，延迟生命。临床常用的筛查方法主要是影像学检查和实验室检查。早诊断、早治疗，是提高卵巢癌治疗效果，改善患者预后，节约社会资源的迫切需求。
目前针对卵巢癌的诊断手段主要分为细胞学和组织病理学检查、影像学检查、血清肿瘤标志物检查。
1、细胞学和组织病理学检查方法
组织病理学是诊断的金标准，大多数卵巢癌恶性肿瘤合并腹水或胸腔积液，行腹水或胸腔积液细胞学检查可发现癌细胞。但临床上通常不容易在初诊时通过此方法确诊。
2、影像学检查方法
卵巢癌的主要影像学检查方法包括超声检查(经阴道/经腹超声)、CT扫描(X线计算机断层成像)、MRI扫描等、和核医学影像检查(如正电子发射计算机断层成像PET/CT)等，可以明确肿瘤形态、侵犯范围等，有助于定性诊断。
(1)超声检查
当有肿块时，B超检查的诊断效果是很好的。但有些情况下，B超是无法检查出阳性结果的，比如一些炎症，像宫颈糜烂，还有白带异常、子宫颈的软硬程度等，都是B超不能确定的，只能靠妇科检查才能发现。但是，由于卵巢在盆腔体内的特殊性致使不能像其他妇科疾病一样由妇科检查进行诊断。
(2)腹盆腔CT扫描
一般来说，CT对所有器质性疾病都可以进行检查，尤其对密度差异大的器质性占位病变都能检查出来并做出定性诊断，腹盆腔CT扫描是卵巢癌最常用的检查方法，可观察病变内微小脂肪、钙化，有助于对卵巢生殖细胞来源肿瘤的检出，但CT对于早期卵巢癌、卵巢形态未发生显著改变者敏感度较低。但最适于CT检查的病是脑部疾病，其中对肿瘤、出血及梗塞等病检查效果最好，其次是腹部实质脏器的占位病变，如肝、脾、胰、肾、前列腺等部位的肿瘤，对乳腺、甲状腺等部位的肿块也能显示并做出诊断；再其次则是对胸腔、肺、心腔内的肿块，脊柱、脊髓、盆腔、胆囊、子宫等部位的肿块检查。一般短时间接受小量X线照射，不会对人体产生大的损害，对人体健康无影响。但长时间反复照射，可对人体产生不良影响，如头痛、头晕、失眠、记忆减退、白细胞数减少等。MRI、CT检查发现脏器有肿瘤时，是良性还是恶性很难做出判断且难以发现≤1CM肿瘤等缺点。
(3)盆腔MRI
软组织分辨率高，其多参数、动态增强扫描可显示病变的组织成分性质和血流动力学特点，对于脂肪、出血等成分的观察有优势，其鉴别卵巢良恶性肿瘤的准确度可达83％～91％；MRI有助于确定盆腔肿块起源，并辅助CT进行卵巢癌的术前分期。卵巢癌原发灶的MRI影响特点与CR相似，以囊实性肿块、不规则囊壁及分隔、乳头结节及不均匀强化为主要特点，但MRI扫描范围有限，且对因运动引起的位移敏感，因此对腹膜转移和大量腹水患者显示效果不如CT。
(4)PET-CT
PET-CT是先进的功能影像学检查手段，能够反应病灶的代谢状况，治疗前PET-CT显像有助于卵巢癌良恶性的鉴别诊断，有利于发现隐匿的转移灶，使分期更准确，通过一次检查能够全面评价淋巴结转移及远处器官的转移；因PET功能影像不受解剖结构的影响，可准确显示解剖结构发生变化后或者是解剖结构复杂部位的复发转移灶；疗效评价，对于抑制肿瘤活性的靶向药物，疗效评价更加敏感、准确；指导放疗生物靶区的勾画、穿刺活检部位；评价肿瘤的恶性程度和预后。缺点在于设备昂贵，检测费用高。
3、肿瘤标志物检查方法
所谓的肿瘤标志物指的是肿瘤细胞异常产生的物质，或者是由于机体对肿瘤的刺激反应而产生的物质，是目前广泛用于肿瘤诊断，同时也是检测肿瘤复发、转移以及评价疗效的重要手段。临床上常见的卵巢癌肿瘤标志物是糖类抗原125(CA125)。但是，肿瘤标记物并非特异性表达在肿瘤组织中，一些良性疾病如盆腔炎症、糖尿病、慢性肾病、胆石症等非肿瘤疾病也会导致一些肿瘤标志物升高；正常女性的怀孕、衰老等正常生理状态也会引起肿瘤标志物升高。此外，在实际情况上，没有任何一种肿瘤标志物的灵敏度和特异性可以精准到100％。例如，黏液性卵巢癌患者仅12％的患者CA125升高，而生殖细胞和性腺细胞肿瘤的患者表达CA125很少甚至不表达率高达20％。与此同时，1％～5％的正常人及一些其他妇科疾病(良性及交界性卵巢肿瘤，宫颈癌，子宫肌瘤，慢性盆腔炎、输卵管炎等)CA125水平均显示超过正常水平；另外，由于CA125也会在一些炎性细胞表达，故在部分风湿性关节炎、系统性红斑狼疮等风湿免疫性疾病中也有不同程度的升高。另外，特别要注意一点的是，妇女月经周期及激素替代治疗等都会影响CA125表达。肿瘤标志物也只有多次动态检测才能表现身体变化，单次单独一项数据都没有没有准确的意义。需要注意的是，一个肿瘤标志物可能对应好几种肿瘤，而目前肿瘤的最终诊断，标志物只是一个参考项目，金标准仍然是病理学诊断加影像学检查。
发明内容
本发明的目的在于：针对现有技术中存在的不足，提供一种卵巢癌外周血TCR标志物及其检测试剂盒和应用，以便准确快速的判断待测样本中是否有较高卵巢癌风险患者。
为实现上述目的，本发明所采用的技术方案是：
一种卵巢癌外周血TCR标志物，TCR标志物包括序列为SEQ ID NO.1～100所示蛋白中的至少一种。
表1标志物序列
进一步地，TCR标志物的蛋白序列为SEQ ID NO.1～100所示的序列经取代、缺失和/或替换一个或多个碱基后，能表达相同功能的蛋白。
上述TCR标志物在制备治疗卵巢癌的制剂中的应用。
进一步地，制剂包括含有该TCR标志物的T细胞受体，或能表达产生该TCR标志物的T细胞受体的质粒、病毒载体或核酸片段。
一种用于卵巢癌检测的试剂盒，包括能与上述卵巢癌外周血TCR标志物发生特异性结合的抗体。
一种制剂，包括能与上述卵巢癌外周血TCR标志物发生特异性结合的抗体；制剂可用于对卵巢癌进行诊断、预测、检测或筛查。
一种检测卵巢癌的蛋白质芯片，蛋白质芯片包括基片和点样在基片上特异性抗体，特异性抗体为能与上述卵巢癌外周血TCR标志物发生特异性结合的抗体。
本发明的原理为：人体内的B淋巴细胞和T淋巴细胞是获得性免疫系统中重要的两类细胞。B细胞通过细胞表面的B细胞受体(BCR)识别抗原，后期BCR在B细胞分化成浆细胞时，表达成抗体，分泌到细胞外。T细胞通过细胞表面的T细胞受体(TCR)识别抗原。BCR和TCR的多样性是建立获得性免疫系统的基础。BCR多样性的理论值是1018，TCR多样性的理论值是1014。BCR与TCR序列中，抗原决定簇3(CDR3)是决定其抗原特异性最重要的部分，因此CDR3的序列被认为可以代表BCR、TCR序列的特性。
在各种疾病中，随着不同的抗原刺激，BCR和TCR的多样性或者表达水平都会发生改变。因此，利用BCR或者TCR高通量测序结果可以追踪疾病的发生、发展。人体内细胞中，衰老蛋白质降解后，其片段会被运输到细胞表面，通过组织相容性抗原II(MCHII)呈递给免疫系统中的T细胞。正常细胞呈递的抗原片段，由于免疫耐受的关系，不会引起免疫反应。一旦当正常细胞出现癌变后，突变的基因表达的异常蛋白，其片段被呈递到细胞表面后，就会引起人体免疫系统产生针对性的免疫反应。因此，分析BCR或TCR的变化，能够检测出肿瘤的发生和发展。
基于高通量测序分析外周血TCR序列以检测是否患有卵巢癌，具体步骤如下：
(1)采集受试者和对照组外周血，通过高通量测序得到受试者和对照组的TCR的抗原决定簇3(CDR3)氨基酸序列，保证每个样本的功能性TCR的CDR3序列总数综合不低于30000；
(2)对每个样本的TCR的CDR3序列进行随机不放回抽样，使每个样本的CDR3序列数量总和均为30000。对任一特定CDR3序列X，在该样本中重复出现次数计为CX；
(3)TCR CDR3数据分析：通过分析确定卵巢癌TCR标志物CDR3序列：
a)将对照组样本所有CDR3序列归总、去重，设为对照序列集；
b)将卵巢癌样本所有CDR3序列归总、去重，再去除所有与对照序列集中包含CDR3序列重复的序列，设为卵巢癌特征序列集；
c)将卵巢癌特征序列集中，出现于两个及以上样本中的CDR3序列，按“在所有卵巢癌样本中该序列重复出现次数CX的总和×包含该序列的卵巢癌样本数”从高到低排序，排名前100者即为卵巢癌TCR标志物CDR3序列。
(4)利用卵巢癌特征性指数判断未知受试者罹患卵巢癌风险：
a)根据健康对照组、非肿瘤病人、非卵巢癌肿瘤患者、卵巢癌患者以及未知健康状况受试者的免疫图谱，分析其卵巢癌特征性指数。
其中卵巢癌特征性指数定义为：某个样本中，属于卵巢癌特征序列集的所有CDR3序列在该样本内重复出现次数CX的总和。
b)当未知健康状况受试者的卵巢癌特征性指数高于或接近“其它肿瘤”组的平均值+2×SD时，此人具有较高风险罹患卵巢癌；如其卵巢癌特征指数接近健康人或非肿瘤疾病组平均值，则表明其患卵巢癌风险低。
综上所述，由于采用了上述技术方案，本发明的有益效果是：
1、本发明中，首先利用1300个非卵巢癌的对照组样本、和100个卵巢癌病人的TCR高通量测序数据建立了人工智能分析模型，通过和这些卵巢癌特异性TCR序列对比，可以清楚的判断待测样本中是否有较高卵巢癌风险者；
2、通过高通量测序分析TCR变化可以发现很早期的卵巢癌，利用卵巢癌特有的TCRCDR3序列分析人的免疫系统中的T细胞对卵巢癌的反应，是一种新型的检测方法；
3、本发明中，由于采用高通量测序技术，同时比较巨大数量的特异性TCR序列，比起单独检测一种或几种标记物，具有更高的特异性和准确性；
4、本发明中使用的高通量测序仪器成本低于大型影像学设备，且可向第三方外包，此外，采样、处理的人力成本低于同时检测多种标记物，也低于大量细胞学检测，因此，本发明大大降低了检测成本；
5、本发明只需要采取少量外周血，采样简便、安全；
6、本发明中所述TCR CDR3序列，可用于卵巢癌的免疫治疗。
附图说明
图1为本发明中，对照组CDR3序列及卵巢癌特征序列。横坐标代表某一特定氨基酸组合的CDR3序列被加入对照序列集合或卵巢癌特征序列集合的先后顺序,纵坐标代表该序列在某一样本中重复出现次数CX的对数值；卵巢癌患者的免疫图谱具有多个种类且重复次数较高的卵巢癌特征序列，健康人极少卵巢癌特征序列，而未知受试者的卵巢癌特征比较明显，说明罹患卵巢癌风险较高。
图2为本发明中，针对卵巢癌特征序列集，计算健康人、非肿瘤病人、非卵巢癌肿瘤患者和卵巢癌患者的卵巢癌特征性指数，健康人、非肿瘤病人、非卵巢癌肿瘤患者的卵巢癌特征性指数均与卵巢癌患者具有显著差异，证明了卵巢癌特征序列集的特异性。据此可以判断未知受试者是否罹患卵巢癌。
具体实施方式
为了使本发明的目的、技术方案及优点更加清楚明白，以下结合附图及实施例，对本发明进行进一步详细说明。应当理解，此处所描述的具体实施例仅用以解释本发明，并不用于限定本发明，即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。通常在此处附图中描述和示出的本发明实施例的组件可以以各种不同的配置来布置和设计。因此，以下对在附图中提供的本发明的实施例的详细描述并非旨在限制要求保护的本发明的范围，而是仅仅表示本发明的选定实施例。基于本发明的实施例，本领域技术人员在没有做出创造性劳动的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。以下结合实施例对本发明的特征和性能作进一步的详细描述。
实施例1：通过免疫图谱分析，获得卵巢癌TCR标志物CDR3序列集
1、采样及免疫图谱分析
采集1301名对照组(包括健康人和非肿瘤疾病病人，1300人用于建立模型，1个健康人用于验证)、101名卵巢癌患者(100人用于建立模型，1人用于验证)及1名未知健康状况受试者的外周血(每人10mL)，通过高通量测序得到受试者和对照组的TCR的抗原决定簇3(CDR3)氨基酸序列，保证每个样本的功能性TCR的CDR3序列总数综合不低于30000；
2、对每个样本的TCR的CDR3序列进行随机不放回抽样，使每个样本的CDR3序列数量总和均为30000。对任一特定CDR3序列X，在单样本测序结果中重复出现次数计为CX；
3、通过分析TCR CDR3数据，确定卵巢癌TCR标志物CDR3序列：
a)将1300名用于建立模型的对照组样本的所有CDR3序列归总去重，设为对照序列集；
b)将100名用于建立模型的卵巢癌样本的所有CDR3序列归总去重，再去除所有与对照序列集中包含序列重复的序列，设为卵巢癌特征序列集。作图如附图1A所示，其中横坐标代表某一特定氨基酸组合的CDR3序列被加入对照序列集合或卵巢癌特征序列集合的先后顺序,纵坐标代表该序列在某一样本中重复出现次数CX的对数值。
c)按照同样作图方法，将1名健康人、1名卵巢癌患者和1名健康状况未知受试者的免疫图谱，参照对照序列集合和卵巢癌特征序列集合进行作图，见附图1B-D。从图中可见，卵巢癌患者的免疫图谱中，含有较多种类且较高重复出现次数的卵巢癌特征序列；健康人的免疫图谱中，只有极少量卵巢癌特征序列；而未知健康状况受试者，有高于健康人的卵巢癌特征序列，说明此人有较高风险罹患卵巢癌。
d)将卵巢癌特征序列集中，将所有出现在两个及以上参与建模卵巢癌样本里的CDR3序列，按“所有参与建模卵巢癌样本里该序列单样本中重复出现次数CX的总和×包含该序列的参与建模卵巢癌样本数”从高到低排序，排名前100者即为卵巢癌TCR标志物CDR3序列，具体序列如SEQ ID NO.1～100所示。
实施例2：验证卵巢癌TCR标志物CDR3序列集的特异性
1、采样及免疫图谱分析
采集250名非卵巢癌的肿瘤患者、107名未知健康状况受试者的外周血(每人10mL)，通过高通量测序得到受试者和对照组的TCR的抗原决定簇3(CDR3)氨基酸序列，保证每个样本的功能性TCR的CDR3序列总数综合不低于30000；对每个样本的TCR的CDR3序列进行随机不放回抽样，使每个样本的CDR3序列数量总和均为30000。
2、从实施例1的对照组中随机挑选100名健康人及45名非肿瘤疾病病人。
3、根据来自实施例1的100名健康人、45名非肿瘤疾病病人、100名卵巢癌患者，以及实施例2新获取的250名非卵巢癌肿瘤患者、107名未知健康状况受试者的免疫图谱，分析其卵巢癌特征性指数。
其中卵巢癌特征性指数定义为：某个样本中，属于卵巢癌特征序列集的所有CDR3序列在该样本内重复出现次数CX的总和。
分析结果见下表2及附图2。卵巢癌组与健康人(p＝6.6E-113)、非肿瘤疾病(p＝1.3E-68)、其它肿瘤(p＝1.9E-188)都有显著差异，这证明了卵巢癌特征序列集的特异性。
表2、不同样本组的卵巢癌特征性指数
4、分析各组的卵巢癌特征指数(表3)，未知健康状况受试者(检测样本)中，前42人的卵巢癌特征指数高于或接近“其它肿瘤”组的平均值+2×SD(590+2×1184＝2958)，此42人具有较高风险罹患卵巢癌；后65人卵巢癌特征指数接近健康人或非肿瘤疾病组平均值，罹患卵巢癌风险低。与临床体检结果对照后，前42人确为卵巢癌患者，而后65人为健康人。此实施例证明了利用卵巢癌特征序列集及卵巢癌特征性指数，预测受试者罹患卵巢癌风险的可行性。
综上所述，本发明所述卵巢癌TCR标志物CDR3序列，确实具有显著的卵巢癌特异性，不仅可以用于卵巢癌预测受试者罹患卵巢癌风险，未来还可用于卵巢癌的生物免疫治疗。
表3、卵巢癌特征性指数分析
| 健康人 | 非肿瘤疾病 | 其他肿瘤 | 卵巢癌 | 检测样本 | |
| Mean | 107.33 | 104.38 | 590.33 | 13153.74 | 3437.03 |
| SD | 41.58 | 77.04 | 1183.67 | 2653.72 | 3509.90 |
| mean+2SD | 190.48 | 258.46 | 2957.67 |
综上所述，本发明所述卵巢癌外周血TCR标志物，确实具有显著的卵巢癌特异性，不仅可以用于卵巢癌预测受试者罹患卵巢癌风险，未来还可用于卵巢癌的生物免疫治疗。
序列表
<110> 成都益安博生物技术有限公司
<120> 一种卵巢癌的外周血TCR标志物及其检测试剂盒和应用
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Ala Ser Ser His Gly Gly Arg Gly Gly Tyr Thr
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Ala Ser His Pro Glu Thr Gly Trp Gly Val Asn Glu Gln Phe
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Ala Ser Ser Leu Val Asn Phe Ser Asn Gln Pro Gln His
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Ala Ser Ser Ser Ser Gly Thr Gly Val Arg Tyr Glu Gln Tyr
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Ala Ser Ser Pro Glu Lys Gly Leu Asn Tyr Gly Tyr Thr
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Gln Gln Pro Glu Arg Glu Ser Gly Asp Pro Val
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Ala Ser Ser Asn Ile Val Glu Gly Thr Asp Thr Gln Tyr
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Ala Ser Ser Ser Arg Tyr Phe Ser Gly Asn Thr Ile Tyr
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Ala Ser Ser Gly Leu Gly Gly Ser Gly Glu Gly Glu Gln Phe
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Ala Ser Ser Leu Val Val Leu Gly Val Arg Leu Asn Thr Gly Glu Leu
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Ala Ser Ser Pro Arg Thr Ser Ala Arg Gly Gly Glu Leu Phe
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Ala Ser Arg Asp Arg Asp Ser Gly Pro Asn Thr Glu Ala Phe
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Ala Ser Ser Pro Ser Gly Ser Gly Ser Gly Gln Pro Gln His
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Ala Ser Ser Leu Gly Gly Leu Val Ala Gln Tyr
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Ala Ser Ser Ala Ser Glu Glu Glu Tyr Lys Tyr Thr Gln Tyr
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Ala Ser Ser Gly Thr Val Leu Ser Tyr Asn Ser Pro Leu His
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Ala Ser Thr Ala Arg Gly Ala Ser Asp Thr Glu Ala Phe
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Ser Ser Val Ser Pro Arg Asp Phe Gln Gly Glu Gln Tyr
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Ala Ser Arg Pro Arg Ile Leu Ala Gln Ala Tyr Asn Glu Gln Phe
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Ala Ser Ser Arg Tyr Ala Trp Arg Asp Asp Glu Gln Phe
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Ala Ser Ser Thr Ser Trp Gly Gly Ala Ser Glu Ala Phe
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Ala Ser Ser Val Ser Pro Ser Gly Ser His Glu Gln Tyr
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<211> 13
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Gln Gln Leu Arg Gln Ala Val Val His Arg Tyr Ala Val
1 5 10
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Ala Pro Trp Leu Arg Asp Arg Asp Ser Tyr Asn Glu Gln Phe
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Ala Ser Thr Ser Arg Gln Thr Met Asp Glu Gln Phe
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Ala Ser Ile Trp Glu Ser Asn Gln Pro Gln His
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<211> 13
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Ala Ser Thr Phe Ser Gly Ser Gly Ala Asn Glu Gln Phe
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<213> 人工序列(Artificial Sequence)
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Ala Ser Ser Pro Gly Asp Ser Val Phe Ser Gly Ala Asn Val Leu Thr
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<211> 12
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Ala Ser Gly Arg Ala Gly Tyr Gly Lys Glu Gln Tyr
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<213> 人工序列(Artificial Sequence)
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Ala Ser Ser Ala Thr Val Ser Tyr Leu Asn Glu Gln Phe
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<213> 人工序列(Artificial Sequence)
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Ala Ser Ser Pro Gly Trp Leu Ala Gly Asp Asp Glu Gln Phe
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Ala Ser Ser Pro Lys Thr Arg Arg Asn Glu Gln Phe
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<213> 人工序列(Artificial Sequence)
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Ala Ser Ser Gln Asp Phe Arg Asp Arg Gly Tyr Glu Thr Gln Tyr
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<210> 48
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 48
Gln Gln Leu Gly Ala Leu Glu Arg Ala Val
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<210> 49
<211> 11
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<213> 人工序列(Artificial Sequence)
<400> 49
Ala Ser Ser Glu Trp Thr Val Gly Glu Gln Phe
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<211> 13
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<400> 50
Ala Ser Ser Pro Pro Gln Gly Thr Pro Tyr Glu Gln Tyr
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Ala Ser Ser Leu Gly Gln Ile Val Pro Glu Ala Phe
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Ala Ser Ser Leu Val Ala Ala Ala His Tyr Gly Tyr Thr
1 5 10
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<211> 11
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<213> 人工序列(Artificial Sequence)
<400> 53
Ala Ser Arg Gly Gln Val Ala Gly Glu Leu Phe
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<400> 54
Ala Ser Ser Asp Arg Tyr Ser Thr Val Gly Asn Gln Pro Gln His
1 5 10 15
<210> 55
<211> 13
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 55
Ala Ser Arg Gly Gly Phe Gln Ile Leu Asp Glu Gln Phe
1 5 10
<210> 56
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 56
Ala Ser Ser Leu Gly Gln Lys Gly Asp Gln Tyr
1 5 10
<210> 57
<211> 13
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<213> 人工序列(Artificial Sequence)
<400> 57
Ser Ala Thr Leu Ser Gly Thr Thr Tyr Asn Glu Gln Phe
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Ala Ser Ser Tyr Leu Ala Gly Gly Pro Val Pro Gln Tyr
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Ala Ser Ser Leu Phe Leu Gly Val Asp Glu Gln Phe
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Ser Ala Arg Ala Gln Gly Phe Asp Gln Pro Gln His
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<211> 15
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Ala Ser Arg Thr Arg Thr Ser Gly Gly Arg Thr Asp Thr Gln Tyr
1 5 10 15
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<211> 9
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<213> 人工序列(Artificial Sequence)
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Ala Ser Ser Glu Thr Glu Ala Gln His
1 5
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<213> 人工序列(Artificial Sequence)
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Ala Ser Ser Gln Glu Glu Thr Gly Arg Gln Pro Gln His
1 5 10
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<213> 人工序列(Artificial Sequence)
<400> 64
Ala Ser Thr Arg Leu Gly Thr Gly His Asn Tyr Gly Tyr Thr
1 5 10
<210> 65
<211> 12
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 65
Pro Ala Ala Arg Ala Gly Val Trp Arg Pro Ser Thr
1 5 10
<210> 66
<211> 17
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 66
Ala Ser Ser Gln Gly Pro Asp Ile Ala Gly Leu Arg Asn Tyr Gly Tyr
1 5 10 15
Thr
<210> 67
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<212> PRT
<213> 人工序列(Artificial Sequence)
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Gln Gln Pro Pro Arg Gln Lys Leu Arg Ala Val
1 5 10
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<213> 人工序列(Artificial Sequence)
<400> 68
Ala Ser Ser Leu Asp Gly Lys Gly Met Ala Phe
1 5 10
<210> 69
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Ala Ser Ser Leu Thr Ser Gly Thr Gly Asp Ser Pro Leu His
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Ala Ser Ser Ser Leu Glu Gly Trp Gly Asp Thr Gln Tyr
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<211> 21
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Ala Ser Ser Leu Ser Tyr Arg Arg Gly Arg Gly Val Ser Tyr Pro Thr
1 5 10 15
Gln Glu Thr Gln Tyr
20
<210> 72
<211> 10
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<400> 72
Ser Val Thr Gly Thr Leu Asp Glu Gln Phe
1 5 10
<210> 73
<211> 16
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 73
Ala Ser Ser Pro Arg Glu Glu Arg Thr Gly Arg Asn Gln Pro Gln His
1 5 10 15
<210> 74
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 74
Ala Thr Gly Leu Ala Phe Ser Tyr Glu Gln Tyr
1 5 10
<210> 75
<211> 16
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 75
Thr Ser Ser Gln Glu Ser Thr Gln Ala Gly Asp Thr Asp Thr Gln Tyr
1 5 10 15
<210> 76
<211> 15
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<400> 76
Ala Ser Ser Phe Leu Pro Gly Gln Gly Leu Asn Thr Glu Ala Phe
1 5 10 15
<210> 77
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<400> 77
Ala Ser Lys Val Ser Gly Thr Ser Gly Arg Glu Thr Gln Tyr
1 5 10
<210> 78
<211> 11
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<400> 78
Gln Gln Leu Pro Arg Ser Val Phe Thr Pro Pro
1 5 10
<210> 79
<211> 12
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<400> 79
Ala Ser Arg Ala Gly Asp Glu Gln Glu Thr Gln Tyr
1 5 10
<210> 80
<211> 15
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<400> 80
Ala Ser Ser Leu Ala Ile Ala Ser Ser Gly Val Asn Glu Gln Phe
1 5 10 15
<210> 81
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<400> 81
Ala Ser Ser Glu Asn Arg Asp Ser Thr Ser Tyr Glu Gln Tyr
1 5 10
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<400> 82
Ala Ser Ser Thr Pro Lys Thr Leu Val Thr Asp Thr Gln Tyr
1 5 10
<210> 83
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<400> 83
Ser Ala Arg Val Pro Ala Glu Gly Gly Asn Ile Gln Tyr
1 5 10
<210> 84
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<400> 84
Ser Ala Arg Pro Thr Ser Gly Arg Leu Lys Val Gly Glu Gln Tyr
1 5 10 15
<210> 85
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<400> 85
Ala Ser Ser Pro His Asp Tyr Gln Glu Leu Asp Thr Asp Thr Gln Tyr
1 5 10 15
<210> 86
<211> 13
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<400> 86
Ala Ser Ser Leu Gly Gly Leu Arg Thr Thr Glu Ala Phe
1 5 10
<210> 87
<211> 11
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<400> 87
Gln Gln Pro Arg Ser Arg Gly Glu His His Ile
1 5 10
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<400> 88
Gln Gln Leu Leu Arg Asp Arg Gly Glu Val Arg Ala Val
1 5 10
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<400> 89
Ala Ser Ser Ser Gly Gly Gly Ile Val Ser Tyr Thr
1 5 10
<210> 90
<211> 14
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<213> 人工序列(Artificial Sequence)
<400> 90
Ala Ser Ser Leu Thr Pro Asp Arg Arg Asp Thr Glu Ala Phe
1 5 10
<210> 91
<211> 14
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<213> 人工序列(Artificial Sequence)
<400> 91
Ala Ser Gly Pro Gly Gln Gly Val Val Gly Asp Gly Tyr Thr
1 5 10
<210> 92
<211> 13
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 92
Ala Ser Ser Met Gly Pro Gly Met Val Gly Gly Tyr Thr
1 5 10
<210> 93
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<400> 93
Ala Ser Gly Thr Ser Gly Thr Gly Leu Cys Gly Tyr Thr
1 5 10
<210> 94
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<400> 94
Ala Ser Ser Pro Arg Trp Thr Lys Asp Tyr Glu Gln Tyr
1 5 10
<210> 95
<211> 11
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<400> 95
Ala Arg Thr Gly Glu Gly Thr Gly Glu Leu Phe
1 5 10
<210> 96
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<400> 96
Ala Ser Ser Arg Ala Gly Thr Gly Ala Gly Asp Thr Gln Tyr
1 5 10
<210> 97
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<400> 97
Ala Ser Arg Arg Gly Gln Gly Lys Ser Gln Pro Gln His
1 5 10
<210> 98
<211> 12
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 98
Gln Gln Phe Leu Ser Gly Gly His Arg Tyr Ala Val
1 5 10
<210> 99
<211> 14
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 99
Ala Thr Val Met Gly Thr Gly Pro Ser Thr Asp Thr Gln Tyr
1 5 10
<210> 100
<211> 14
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 100
Ala Ser Ser Leu Thr Ser Ala Gly Ser Ala Ile Glu Gln Phe
1 5 10
Claims (7)
1.卵巢癌的外周血TCR标志物，其特征在于，所述TCR标志物包括序列为SEQ ID NO.1～100所示蛋白中的至少一种。
2.根据权利要求1所述的卵巢癌的外周血TCR标志物，其特征在于，所述TCR标志物的蛋白序列为SEQ ID NO.1～100所示的序列经取代、缺失和/或替换一个或多个碱基后，能表达相同功能的蛋白。
3.权利要求1所述的卵巢癌的外周血TCR标志物在制备治疗卵巢癌的制剂中的应用。
4.根据权利要求3所述的应用，其特征在于，所述制剂包括含有该TCR标志物的T细胞受体，或能表达产生该TCR标志物的T细胞受体的质粒、病毒载体或核酸片段。
5.一种用于卵巢癌检测的试剂盒，其特征在于，包括能与权利要求1所述卵巢癌的外周血TCR标志物发生特异性结合的抗体。
6.一种制剂，其特征在于，包括能与权利要求1所述卵巢癌的外周血TCR标志物发生特异性结合的抗体。
7.一种检测卵巢癌的蛋白质芯片，其特征在于，所述蛋白质芯片包括基片和点样在基片上特异性抗体，所述特异性抗体为能与权利要求1所述卵巢癌的外周血TCR标志物发生特异性结合的抗体。
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113109564A (zh) * | 2021-03-15 | 2021-07-13 | 成都益安博生物技术有限公司 | 一种急性髓细胞性白血病的外周血tcr标志物及其检测试剂盒和应用 |
| CN113567682A (zh) * | 2021-07-23 | 2021-10-29 | 成都益安博生物技术有限公司 | 一种阿尔茨海默病的外周血tcr标志物及其检测试剂盒和应用 |
| WO2022012289A1 (zh) * | 2020-07-11 | 2022-01-20 | 成都益安博生物技术有限公司 | 一种卵巢癌的外周血tcr标志物及其检测试剂盒和应用 |
| CN114203254A (zh) * | 2021-12-02 | 2022-03-18 | 杭州艾沐蒽生物科技有限公司 | 一种基于人工智能分析免疫特征相关tcr的方法 |
| WO2022194039A1 (zh) * | 2021-03-15 | 2022-09-22 | 成都益安博生物技术有限公司 | 一种急性b淋巴细胞白血病的外周血tcr标志物及其检测试剂盒和应用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013002086A1 (ja) * | 2011-06-28 | 2013-01-03 | 株式会社癌免疫研究所 | ペプチド癌抗原特異的ｔ細胞のレセプター遺伝子 |
| CN104422768A (zh) * | 2013-08-30 | 2015-03-18 | 广州瑞博奥生物科技有限公司 | 一种联合检测早期卵巢癌标志物的抗体芯片试剂盒 |
| DE102016123859B3 (de) * | 2016-12-08 | 2018-03-01 | Immatics Biotechnologies Gmbh | Neue T-Zellrezeptoren und deren Verwendung in Immuntherapie |
| JP7150280B2 (ja) * | 2017-03-15 | 2022-10-11 | 学校法人兵庫医科大学 | がん免疫療法の新規バイオマーカ |
| US11898207B2 (en) * | 2017-03-31 | 2024-02-13 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Methods of isolating neoantigen-specific T cell receptor sequences |
| CN111624342A (zh) * | 2020-07-11 | 2020-09-04 | 成都益安博生物技术有限公司 | 一种卵巢癌的外周血tcr标志物及其检测试剂盒和应用 |
-
2020
- 2020-07-11 CN CN202010665309.8A patent/CN111624342A/zh active Pending
-
2021
- 2021-06-24 WO PCT/CN2021/101947 patent/WO2022012289A1/zh active Application Filing
Non-Patent Citations (5)
| Title |
|---|
| 中国科协学会学术部: "《网络药理学-中药现代化的新思路与新方法》", 30 November 2014, 中国科学技术出版社, pages: 12 - 14 * |
| 王继贤 等: "《临床生化检验（第二版）》", 31 July 1996, 湖南科学技术出版社, pages: 260 - 261 * |
| 程书钧: "《癌前病变和癌前癌症》", 31 January 2017, 河南科学技术出版社, pages: 39 - 40 * |
| 胡智祥: "《医院临床检验技术操作规范与实（化）验室管理全书》", 31 August 2004, 银声音像出版社, pages: 110 - 113 * |
| 董吁钢 等: "《心血管疾病预防与康复》", 28 February 2013, 中山大学出版社, pages: 25 - 26 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022012289A1 (zh) * | 2020-07-11 | 2022-01-20 | 成都益安博生物技术有限公司 | 一种卵巢癌的外周血tcr标志物及其检测试剂盒和应用 |
| CN113109564A (zh) * | 2021-03-15 | 2021-07-13 | 成都益安博生物技术有限公司 | 一种急性髓细胞性白血病的外周血tcr标志物及其检测试剂盒和应用 |
| WO2022194039A1 (zh) * | 2021-03-15 | 2022-09-22 | 成都益安博生物技术有限公司 | 一种急性b淋巴细胞白血病的外周血tcr标志物及其检测试剂盒和应用 |
| CN113567682A (zh) * | 2021-07-23 | 2021-10-29 | 成都益安博生物技术有限公司 | 一种阿尔茨海默病的外周血tcr标志物及其检测试剂盒和应用 |
| WO2023000688A1 (zh) * | 2021-07-23 | 2023-01-26 | 成都益安博生物技术有限公司 | 一种阿尔茨海默病的外周血tcr标志物及其检测试剂盒和应用 |
| CN114203254A (zh) * | 2021-12-02 | 2022-03-18 | 杭州艾沐蒽生物科技有限公司 | 一种基于人工智能分析免疫特征相关tcr的方法 |
| CN114203254B (zh) * | 2021-12-02 | 2023-05-23 | 杭州艾沐蒽生物科技有限公司 | 一种基于人工智能分析免疫特征相关tcr的方法 |
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