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CN112210603A - 组合基因在食管鳞癌中的应用 - Google Patents

组合基因在食管鳞癌中的应用 Download PDF

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CN112210603A
CN112210603A CN202011048576.7A CN202011048576A CN112210603A CN 112210603 A CN112210603 A CN 112210603A CN 202011048576 A CN202011048576 A CN 202011048576A CN 112210603 A CN112210603 A CN 112210603A
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袁勇
刘博�
张寿悦
栾思源
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West China Hospital of Sichuan University
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Abstract

本发明涉及生物医药技术领域，公开了组合基因在制备诊断食管鳞癌的产品中的应用，所述组合基因包括如下基因：CCL20基因，GSTP1基因，HSPB1基因，KRT14基因，KRT15基因，S100A8基因，S100A9基因，TACSTD2基因；本发明还公开了组合基因在制备治疗食管鳞癌的药物组合物中的应用。本发明与现有技术中食管鳞癌单一基因表达检测相比，本发明具有更高的特异性和更高的诊断效能，可显著提高检测敏感度及特异度，本发明能够准确、便捷、高效进行食管鳞癌早期诊断及大规模筛查，填补了现有诊断技术上的空白，从而更及时的为食管鳞癌患者提供有效治疗措施并改善预后。

Description

组合基因在食管鳞癌中的应用
技术领域
本发明涉及生物医药技术领域，具体涉及组合基因在食管鳞癌中的应用。
背景技术
食管癌(Esophageal cancer，EC)是起源于人食管上皮细胞的消化道恶性肿瘤，主要病理类型为鳞状细胞癌和腺癌。在食管癌发病率逐年上升的同时，其总体5年生存率仅徘徊在15％-25％。中国是食管癌高发国家，食管癌已成为我国最常见的四大恶性肿瘤之一，疾病晚期患者往往出现严重的吞咽困难、营养不良、甚至导致恶病质，严重影响国民身心健康的同时，为社会带来了沉重的疾病负担。
食管癌的不良预后与诊断的延误密切相关，由于食管癌起病隐匿、早期症状不典型、缺乏有效的大规模筛检方法，很多患者在确诊时疾病已进展至中晚期，肿瘤难以彻底切除，且出现不同程度的淋巴结受累和远处转移，为后续治疗带来了极大的困难。目前临床上最常用的食管癌确诊方法为上消化道内镜及活组织病理检查，但这种侵入性检查成本高、操作复杂、会为受检者带来不同程度的不适感，不适于大规模应用。现有的影像学检查例如CT扫描和上消化道钡剂造影也无法满足早期诊断和广泛筛查的需求。传统血清肿瘤标志物则因其较低的敏感性及特异性，在早期诊断食管癌方面能力有限。
测序技术的测序精度已达到单个细胞水平，极大地推动了人们对癌症在基因层面的进一步认知。食管癌是一种由多基因驱动、多因素调控的复杂疾病，在疾病演进过程中存在基因组、转录组、蛋白组等多水平产物的改变。这种改变在一定程度上具有明显的肿瘤特异性，因此可以用于疾病的检测。大量研究发现，经过筛选得到的一组生物标志物联合应用于疾病诊断，可以弥补单一生物标志物特异性差、诊断效能低的缺点，从而显著提高检测敏感度及特异度。因此，申请人借助高通量组学技术进行前期筛选，研发一种能够准确、便捷、高效进行食管癌早期诊断及大规模筛查的诊断工具，以填补现有诊断技术上的空白，从而更及时的为食管癌患者提供有效治疗措施并改善预后。
发明内容
基于以上问题，本发明提供组合基因在食管鳞癌中的应用，本发明能够准确、便捷、高效进行食管鳞癌早期诊断及大规模筛查，填补了现有诊断技术上的空白，从而能更及时的为食管鳞癌患者提供有效治疗措施并改善预后。
为解决以上技术问题，本发明提供了组合基因在制备诊断食管鳞癌的产品中的应用，所述组合基因包括如下基因：CCL20基因，GSTP1基因，HSPB1基因，KRT14基因，KRT15基因，S100A8基因，S100A9基因，TACSTD2基因。
进一步的，所述产品可与下列任意一种检测方式相结合来诊断食管鳞癌：RT-PCR、实时定量PCR、免疫检测、原位杂交、芯片检测、高通量测序平台检测。
进一步的，所述产品包括检测样本中CCL20基因表达的蛋白、GSTP1基因表达的蛋白、HSPB1基因表达的蛋白、KRT14基因表达的蛋白、KRT15基因表达的蛋白、S100A8基因表达的蛋白、S100A9基因表达的蛋白、TACSTD2基因表达的蛋白的试剂。
进一步的，所述产品包括芯片或试剂盒；其中，所述芯片包括基因芯片、蛋白质芯片；所述试剂盒包括基因检测试剂盒、蛋白免疫检测试剂盒。
为解决以上技术问题，本发明还提供了组合基因在制备治疗食管鳞癌的药物组合物中的应用。
进一步的，所述药物组合物包括增加组合基因表达、增强组合基因表达功能、和/或增强组合基因表达产物活性的试剂。
进一步的，所述试剂包括：含有能编码功能性组合基因分泌蛋白的核酸的试剂、组合基因分泌蛋白的激活剂、含有组合基因分泌蛋白质的试剂。
进一步的，所述药物组合物还包括药学上可接受的载体。
与现有技术相比，本发明的有益效果是：本发明筛选获得了一组与食管鳞癌的发生相关的组合基因，与现有技术中食管鳞癌单一基因表达检测相比，本发明具有更高的特异性和更高的诊断效能，可显著提高检测敏感度及特异度，本发明能够准确、便捷、高效进行食管鳞癌早期诊断及大规模筛查，填补了现有诊断技术上的空白，从而更及时的为食管鳞癌患者提供有效治疗措施并改善预后；本发明具有良好的临床应用价值，能够解决当前食管鳞癌早期诊断及大规模筛查方式有限的问题，有助于推动食管鳞癌的早诊早治并改善患者远期预后，以期缓解社会疾病负担。
附图说明
图1为本发明的实施例中CCL20基因分泌蛋白在食管鳞癌患者中和健康对照者的血清中的浓度对照结果图；
图2为本发明的实施例中GSTP1基因分泌蛋白在食管鳞癌患者中和健康对照者的血清中的浓度对照结果图；
图3为本发明的实施例中HSPB1基因分泌蛋白在食管鳞癌患者中和健康对照者的血清中的浓度对照结果图；
图4为本发明的实施例中KRT14基因分泌蛋白在食管鳞癌患者中和健康对照者的血清中的浓度对照结果图；
图5为本发明的实施例中KRT15基因分泌蛋白在食管鳞癌患者中和健康对照者的血清中的浓度对照结果图；
图6为本发明的实施例中S100A8基因分泌蛋白在食管鳞癌患者中和健康对照者的血清中的浓度对照结果图；
图7为本发明的实施例中S100A9基因分泌蛋白在食管鳞癌患者中和健康对照者的血清中的浓度对照结果图；
图8为本发明的实施例中TACSTD2基因分泌蛋白在食管鳞癌患者中和健康对照者的血清中的浓度对照结果图。
具体实施方式
为使本发明的目的、技术方案和优点更加清楚明白，下面结合实施例和附图，对本发明作进一步的详细说明，本发明的示意性实施方式及其说明仅用于解释本发明，并不作为对本发明的限定。
实施例：
本实施例收集在四川大学华西医院胸外科就诊的原发性食管鳞癌病人(经病理诊断)癌和癌旁组织样本，上述操作经过了病人同意以及机构审查委员会和医院伦理委员会批准。样本离体后快速低温运输并消化获得食管鳞癌单细胞悬液用于上机测序。本实施例最终收集了11例食管鳞癌患者的癌和癌旁样本，均为男性患者。
本实施例做了用于进行ELISA间接法实验的血清样本的准备工作，具体如下：
(1)收集四川大学华西医院原发性食管癌病人(食管癌经病理诊断)的标本，所有标本均用红头釆血管采集研究对象全血
Figure BDA0002708790240000041
将收集于血清分离管中的全血标本在室温放置2小时，然后1000g离心20分钟，取上清于-80摄氏度保存，避免反复冻融；
(2)来自四川大学华西医院的食管鳞癌患者中，既有男性也有女性，所有对照组血清均来自新发食管鳞癌患者，且无新辅助放化疗史，正常人血清来自参加年度健康体检，无任何恶性肿瘤症状的体检人群。
发明人利用单细胞测序筛选食管鳞癌诊断生物标志物，最终筛选出如下八个基因：CCL20基因，GSTP1基因，HSPB1基因，KRT14基因，KRT15基因，S100A8基因，S100A9基因，TACSTD2基因。
发明人利用ELISA间接实验法验证了上述八个基因所对应的分泌蛋白在食管鳞癌患者和健康对照者的血清中的浓度，对照结果图见附图1、附图2、附图3、附图4、附图5、附图6、附图7和附图8，其中纵坐标中的concentration代表浓度，NC为健康对照组，ESCC为食管鳞癌患者组，结果显示，食管鳞癌患者中的CCL20基因、GSTP1基因、HSPB1基因、KRT14基因、KRT15基因、S100A8基因、S100A9基因、TACSTD2基因等分泌蛋白表达量均高于健康对照者。
上述组合基因可应用于制备诊断食管鳞癌的产品中；本实施例的产品可与下列任意一种检测方式相结合来诊断食管鳞癌：RT-PCR、实时定量PCR、免疫检测、原位杂交、芯片检测、高通量测序平台检测；本实施例的产品包括检测样本中CCL20基因表达的蛋白、GSTP1基因表达的蛋白、HSPB1基因表达的蛋白、KRT14基因表达的蛋白、KRT15基因表达的蛋白、S100A8基因表达的蛋白、S100A9基因表达的蛋白、TACSTD2基因表达的蛋白的试剂；本实施例所述芯片包括基因芯片、蛋白质芯片；所述试剂盒包括基因检测试剂盒、蛋白免疫检测试剂盒。
上述组合基因还可应用于制备治疗食管鳞癌的药物组合物中，本实施例的药物组合物包括增加组合基因表达、增强组合基因表达功能、和/或增强组合基因表达产物活性的试剂，本实施例的试剂包括：含有能编码功能性组合基因分泌蛋白的核酸的试剂、组合基因分泌蛋白的激活剂、含有组合基因分泌蛋白质的试剂；本实施例的药物组合物还包括药学上可接受的载体。
如上即为本发明的实施例。上述实施例以及实施例中的具体参数仅是为了清楚表述发明验证过程，并非用以限制本发明的专利保护范围，本发明的专利保护范围仍然以其权利要求书为准，凡是运用本发明的说明书及附图内容所作的等同结构变化，同理均应包含在本发明的保护范围内。
序列表
<110> 四川大学华西医院
<120> 组合基因在食管鳞癌中的应用
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210
<210> 4
<211> 205
<212> PRT
<213> Homo sapiens
<400> 4
Met Thr Glu Arg Arg Val Pro Phe Ser Leu Leu Arg Gly Pro Ser Trp
1 5 10 15
Asp Pro Phe Arg Asp Trp Tyr Pro His Ser Arg Leu Phe Asp Gln Ala
20 25 30
Phe Gly Leu Pro Arg Leu Pro Glu Glu Trp Ser Gln Trp Leu Gly Gly
35 40 45
Ser Ser Trp Pro Gly Tyr Val Arg Pro Leu Pro Pro Ala Ala Ile Glu
50 55 60
Ser Pro Ala Val Ala Ala Pro Ala Tyr Ser Arg Ala Leu Ser Arg Gln
65 70 75 80
Leu Ser Ser Gly Val Ser Glu Ile Arg His Thr Ala Asp Arg Trp Arg
85 90 95
Val Ser Leu Asp Val Asn His Phe Ala Pro Asp Glu Leu Thr Val Lys
100 105 110
Thr Lys Asp Gly Val Val Glu Ile Thr Gly Lys His Glu Glu Arg Gln
115 120 125
Asp Glu His Gly Tyr Ile Ser Arg Cys Phe Thr Arg Lys Tyr Thr Leu
130 135 140
Pro Pro Gly Val Asp Pro Thr Gln Val Ser Ser Ser Leu Ser Pro Glu
145 150 155 160
Gly Thr Leu Thr Val Glu Ala Pro Met Pro Lys Leu Ala Thr Gln Ser
165 170 175
Asn Glu Ile Thr Ile Pro Val Thr Phe Glu Ser Arg Ala Gln Leu Gly
180 185 190
Gly Pro Glu Ala Ala Lys Ser Asp Glu Thr Ala Ala Lys
195 200 205
<210> 5
<211> 472
<212> PRT
<213> Homo sapiens
<400> 5
Met Thr Thr Cys Ser Arg Gln Phe Thr Ser Ser Ser Ser Met Lys Gly
1 5 10 15
Ser Cys Gly Ile Gly Gly Gly Ile Gly Gly Gly Ser Ser Arg Ile Ser
20 25 30
Ser Val Leu Ala Gly Gly Ser Cys Arg Ala Pro Ser Thr Tyr Gly Gly
35 40 45
Gly Leu Ser Val Ser Ser Ser Arg Phe Ser Ser Gly Gly Ala Cys Gly
50 55 60
Leu Gly Gly Gly Tyr Gly Gly Gly Phe Ser Ser Ser Ser Ser Ser Phe
65 70 75 80
Gly Ser Gly Phe Gly Gly Gly Tyr Gly Gly Gly Leu Gly Ala Gly Leu
85 90 95
Gly Gly Gly Phe Gly Gly Gly Phe Ala Gly Gly Asp Gly Leu Leu Val
100 105 110
Gly Ser Glu Lys Val Thr Met Gln Asn Leu Asn Asp Arg Leu Ala Ser
115 120 125
Tyr Leu Asp Lys Val Arg Ala Leu Glu Glu Ala Asn Ala Asp Leu Glu
130 135 140
Val Lys Ile Arg Asp Trp Tyr Gln Arg Gln Arg Pro Ala Glu Ile Lys
145 150 155 160
Asp Tyr Ser Pro Tyr Phe Lys Thr Ile Glu Asp Leu Arg Asn Lys Ile
165 170 175
Leu Thr Ala Thr Val Asp Asn Ala Asn Val Leu Leu Gln Ile Asp Asn
180 185 190
Ala Arg Leu Ala Ala Asp Asp Phe Arg Thr Lys Tyr Glu Thr Glu Leu
195 200 205
Asn Leu Arg Met Ser Val Glu Ala Asp Ile Asn Gly Leu Arg Arg Val
210 215 220
Leu Asp Glu Leu Thr Leu Ala Arg Ala Asp Leu Glu Met Gln Ile Glu
225 230 235 240
Ser Leu Lys Glu Glu Leu Ala Tyr Leu Lys Lys Asn His Glu Glu Glu
245 250 255
Met Asn Ala Leu Arg Gly Gln Val Gly Gly Asp Val Asn Val Glu Met
260 265 270
Asp Ala Ala Pro Gly Val Asp Leu Ser Arg Ile Leu Asn Glu Met Arg
275 280 285
Asp Gln Tyr Glu Lys Met Ala Glu Lys Asn Arg Lys Asp Ala Glu Glu
290 295 300
Trp Phe Phe Thr Lys Thr Glu Glu Leu Asn Arg Glu Val Ala Thr Asn
305 310 315 320
Ser Glu Leu Val Gln Ser Gly Lys Ser Glu Ile Ser Glu Leu Arg Arg
325 330 335
Thr Met Gln Asn Leu Glu Ile Glu Leu Gln Ser Gln Leu Ser Met Lys
340 345 350
Ala Ser Leu Glu Asn Ser Leu Glu Glu Thr Lys Gly Arg Tyr Cys Met
355 360 365
Gln Leu Ala Gln Ile Gln Glu Met Ile Gly Ser Val Glu Glu Gln Leu
370 375 380
Ala Gln Leu Arg Cys Glu Met Glu Gln Gln Asn Gln Glu Tyr Lys Ile
385 390 395 400
Leu Leu Asp Val Lys Thr Arg Leu Glu Gln Glu Ile Ala Thr Tyr Arg
405 410 415
Arg Leu Leu Glu Gly Glu Asp Ala His Leu Ser Ser Ser Gln Phe Ser
420 425 430
Ser Gly Ser Gln Ser Ser Arg Asp Val Thr Ser Ser Ser Arg Gln Ile
435 440 445
Arg Thr Lys Val Met Asp Val His Asp Gly Lys Val Val Ser Thr His
450 455 460
Glu Gln Val Leu Arg Thr Lys Asn
465 470
<210> 6
<211> 456
<212> PRT
<213> Homo sapiens
<400> 6
Met Thr Thr Thr Phe Leu Gln Thr Ser Ser Ser Thr Phe Gly Gly Gly
1 5 10 15
Ser Thr Arg Gly Gly Ser Leu Leu Ala Gly Gly Gly Gly Phe Gly Gly
20 25 30
Gly Ser Leu Ser Gly Gly Gly Gly Ser Arg Ser Ile Ser Ala Ser Ser
35 40 45
Ala Arg Phe Val Ser Ser Gly Ser Gly Gly Gly Tyr Gly Gly Gly Met
50 55 60
Arg Val Cys Gly Phe Gly Gly Gly Ala Gly Ser Val Phe Gly Gly Gly
65 70 75 80
Phe Gly Gly Gly Val Gly Gly Gly Phe Gly Gly Gly Phe Gly Gly Gly
85 90 95
Asp Gly Gly Leu Leu Ser Gly Asn Glu Lys Ile Thr Met Gln Asn Leu
100 105 110
Asn Asp Arg Leu Ala Ser Tyr Leu Asp Lys Val Arg Ala Leu Glu Glu
115 120 125
Ala Asn Ala Asp Leu Glu Val Lys Ile His Asp Trp Tyr Gln Lys Gln
130 135 140
Thr Pro Thr Ser Pro Glu Cys Asp Tyr Ser Gln Tyr Phe Lys Thr Ile
145 150 155 160
Glu Glu Leu Arg Asp Lys Ile Met Ala Thr Thr Ile Asp Asn Ser Arg
165 170 175
Val Ile Leu Glu Ile Asp Asn Ala Arg Leu Ala Ala Asp Asp Phe Arg
180 185 190
Leu Lys Tyr Glu Asn Glu Leu Ala Leu Arg Gln Gly Val Glu Ala Asp
195 200 205
Ile Asn Gly Leu Arg Arg Val Leu Asp Glu Leu Thr Leu Ala Arg Thr
210 215 220
Asp Leu Glu Met Gln Ile Glu Gly Leu Asn Glu Glu Leu Ala Tyr Leu
225 230 235 240
Lys Lys Asn His Glu Glu Glu Met Lys Glu Phe Ser Ser Gln Leu Ala
245 250 255
Gly Gln Val Asn Val Glu Met Asp Ala Ala Pro Gly Val Asp Leu Thr
260 265 270
Arg Val Leu Ala Glu Met Arg Glu Gln Tyr Glu Ala Met Ala Glu Lys
275 280 285
Asn Arg Arg Asp Val Glu Ala Trp Phe Phe Ser Lys Thr Glu Glu Leu
290 295 300
Asn Lys Glu Val Ala Ser Asn Thr Glu Met Ile Gln Thr Ser Lys Thr
305 310 315 320
Glu Ile Thr Asp Leu Arg Arg Thr Met Gln Glu Leu Glu Ile Glu Leu
325 330 335
Gln Ser Gln Leu Ser Met Lys Ala Gly Leu Glu Asn Ser Leu Ala Glu
340 345 350
Thr Glu Cys Arg Tyr Ala Thr Gln Leu Gln Gln Ile Gln Gly Leu Ile
355 360 365
Gly Gly Leu Glu Ala Gln Leu Ser Glu Leu Arg Cys Glu Met Glu Ala
370 375 380
Gln Asn Gln Glu Tyr Lys Met Leu Leu Asp Ile Lys Thr Arg Leu Glu
385 390 395 400
Gln Glu Ile Ala Thr Tyr Arg Ser Leu Leu Glu Gly Gln Asp Ala Lys
405 410 415
Met Ala Gly Ile Ala Ile Arg Glu Ala Ser Ser Gly Gly Gly Gly Ser
420 425 430
Ser Ser Asn Phe His Ile Asn Val Glu Glu Ser Val Asp Gly Gln Val
435 440 445
Val Ser Ser His Lys Arg Glu Ile
450 455
<210> 7
<211> 463
<212> PRT
<213> Homo sapiens
<400> 7
Met Thr Thr Thr Phe Leu Gln Thr Ser Ser Ser Thr Phe Gly Gly Gly
1 5 10 15
Ser Thr Arg Gly Gly Ser Leu Leu Ala Gly Gly Gly Gly Phe Gly Gly
20 25 30
Gly Ser Leu Ser Gly Gly Gly Gly Ser Arg Ser Ile Ser Ala Ser Ser
35 40 45
Ala Arg Phe Val Ser Ser Gly Ser Gly Gly Gly Tyr Gly Gly Gly Met
50 55 60
Arg Val Cys Gly Phe Gly Gly Gly Ala Gly Ser Val Phe Gly Gly Gly
65 70 75 80
Phe Gly Gly Gly Val Gly Gly Gly Phe Gly Gly Gly Phe Gly Gly Gly
85 90 95
Asp Gly Gly Leu Leu Ser Gly Asn Glu Lys Ile Thr Met Gln Asn Leu
100 105 110
Asn Asp Arg Leu Ala Ser Tyr Leu Asp Lys Val Arg Ala Leu Glu Glu
115 120 125
Ala Asn Ala Asp Leu Glu Val Lys Ile His Asp Trp Tyr Gln Lys Gln
130 135 140
Thr Pro Thr Ser Pro Glu Cys Asp Tyr Ser Gln Tyr Phe Lys Thr Ile
145 150 155 160
Glu Glu Leu Arg Asp Lys Ile Met Ala Thr Thr Ile Asp Asn Ser Arg
165 170 175
Val Ile Leu Glu Ile Asp Asn Ala Arg Leu Ala Ala Asp Asp Phe Arg
180 185 190
Leu Lys Tyr Glu Asn Glu Leu Ala Leu Arg Gln Gly Val Glu Ala Asp
195 200 205
Ile Asn Gly Leu Arg Arg Val Leu Asp Glu Leu Thr Leu Ala Arg Thr
210 215 220
Asp Leu Glu Met Gln Ile Glu Gly Leu Asn Glu Glu Leu Ala Tyr Leu
225 230 235 240
Lys Lys Asn His Glu Glu Trp Val Pro Pro Ile Leu Gln Glu Met Lys
245 250 255
Glu Phe Ser Ser Gln Leu Ala Gly Gln Val Asn Val Glu Met Asp Ala
260 265 270
Ala Pro Gly Val Asp Leu Thr Arg Val Leu Ala Glu Met Arg Glu Gln
275 280 285
Tyr Glu Ala Met Ala Glu Lys Asn Arg Arg Asp Val Glu Ala Trp Phe
290 295 300
Phe Ser Lys Thr Glu Glu Leu Asn Lys Glu Val Ala Ser Asn Thr Glu
305 310 315 320
Met Ile Gln Thr Ser Lys Thr Glu Ile Thr Asp Leu Arg Arg Thr Met
325 330 335
Gln Glu Leu Glu Ile Glu Leu Gln Ser Gln Leu Ser Met Lys Ala Gly
340 345 350
Leu Glu Asn Ser Leu Ala Glu Thr Glu Cys Arg Tyr Ala Thr Gln Leu
355 360 365
Gln Gln Ile Gln Gly Leu Ile Gly Gly Leu Glu Ala Gln Leu Ser Glu
370 375 380
Leu Arg Cys Glu Met Glu Ala Gln Asn Gln Glu Tyr Lys Met Leu Leu
385 390 395 400
Asp Ile Lys Thr Arg Leu Glu Gln Glu Ile Ala Thr Tyr Arg Ser Leu
405 410 415
Leu Glu Gly Gln Asp Ala Lys Met Ala Gly Ile Ala Ile Arg Glu Ala
420 425 430
Ser Ser Gly Gly Gly Gly Ser Ser Ser Asn Phe His Ile Asn Val Glu
435 440 445
Glu Ser Val Asp Gly Gln Val Val Ser Ser His Lys Arg Glu Ile
450 455 460
<210> 8
<211> 437
<212> PRT
<213> Homo sapiens
<400> 8
Met Thr Thr Thr Phe Leu Gln Thr Ser Ser Ser Thr Phe Gly Gly Gly
1 5 10 15
Ser Thr Arg Gly Gly Ser Leu Leu Ala Gly Gly Gly Gly Phe Gly Gly
20 25 30
Gly Ser Leu Ser Gly Gly Gly Gly Ser Arg Ser Ile Ser Ala Ser Ser
35 40 45
Ala Arg Phe Val Ser Ser Gly Ser Gly Gly Gly Tyr Gly Gly Gly Met
50 55 60
Arg Val Cys Gly Phe Gly Gly Gly Ala Gly Ser Val Phe Gly Gly Gly
65 70 75 80
Phe Gly Gly Gly Val Gly Gly Gly Phe Gly Gly Gly Phe Gly Gly Gly
85 90 95
Asp Gly Gly Leu Leu Ser Gly Asn Glu Lys Ile Thr Met Gln Asn Leu
100 105 110
Asn Asp Arg Leu Ala Ser Tyr Leu Asp Lys Val Arg Ala Leu Glu Glu
115 120 125
Ala Asn Ala Asp Leu Glu Val Lys Ile His Asp Trp Tyr Gln Lys Gln
130 135 140
Thr Pro Thr Ser Pro Glu Cys Asp Tyr Ser Gln Tyr Phe Lys Thr Ile
145 150 155 160
Glu Glu Leu Arg Asp Lys Ile Met Ala Thr Thr Ile Asp Asn Ser Arg
165 170 175
Val Ile Leu Glu Ile Asp Asn Ala Arg Leu Ala Ala Asp Asp Phe Arg
180 185 190
Leu Lys Tyr Glu Asn Glu Leu Ala Leu Arg Gln Gly Val Glu Ala Asp
195 200 205
Ile Asn Gly Leu Arg Arg Val Leu Asp Glu Leu Thr Leu Ala Arg Thr
210 215 220
Asp Leu Glu Met Gln Ile Glu Gly Leu Asn Glu Glu Leu Ala Tyr Leu
225 230 235 240
Lys Lys Asn His Glu Glu Trp Val Pro Pro Ile Leu Gln Glu Met Lys
245 250 255
Glu Phe Ser Ser Gln Leu Ala Gly Gln Val Asn Val Glu Met Asp Ala
260 265 270
Ala Pro Gly Val Asp Leu Thr Arg Val Leu Ala Glu Met Arg Glu Gln
275 280 285
Tyr Glu Ala Met Ala Glu Lys Asn Arg Arg Asp Val Glu Ala Trp Phe
290 295 300
Phe Ser Lys Thr Glu Glu Leu Asn Lys Glu Val Ala Ser Asn Thr Glu
305 310 315 320
Met Ile Gln Thr Ser Lys Thr Glu Ile Thr Asp Leu Arg Arg Thr Met
325 330 335
Gln Glu Leu Glu Ile Glu Leu Gln Ser Gln Leu Ser Met Lys Ala Gly
340 345 350
Leu Glu Asn Ser Leu Ala Glu Thr Glu Cys Arg Tyr Ala Thr Gln Leu
355 360 365
Gln Gln Ile Gln Gly Leu Ile Gly Gly Leu Glu Ala Gln Leu Ser Glu
370 375 380
Leu Arg Cys Glu Met Glu Ala Gln Asn Gln Glu Tyr Lys Met Leu Leu
385 390 395 400
Asp Ile Lys Thr Arg Leu Glu Gln Glu Ile Ala Thr Tyr Arg Ser Leu
405 410 415
Leu Glu Gly Gln Asp Ala Lys Met Ala Gly Ile Ala Ile Arg Glu Ala
420 425 430
Tyr Ser Phe Ser Leu
435
<210> 9
<211> 93
<212> PRT
<213> Homo sapiens
<400> 9
Met Leu Thr Glu Leu Glu Lys Ala Leu Asn Ser Ile Ile Asp Val Tyr
1 5 10 15
His Lys Tyr Ser Leu Ile Lys Gly Asn Phe His Ala Val Tyr Arg Asp
20 25 30
Asp Leu Lys Lys Leu Leu Glu Thr Glu Cys Pro Gln Tyr Ile Arg Lys
35 40 45
Lys Gly Ala Asp Val Trp Phe Lys Glu Leu Asp Ile Asn Thr Asp Gly
50 55 60
Ala Val Asn Phe Gln Glu Phe Leu Ile Leu Val Ile Lys Met Gly Val
65 70 75 80
Ala Ala His Lys Lys Ser His Glu Glu Ser His Lys Glu
85 90
<210> 10
<211> 117
<212> PRT
<213> Homo sapiens
<400> 10
Met Ser Leu Val Ser Cys Leu Ser Glu Asp Leu Lys Val Leu Phe Phe
1 5 10 15
Arg Trp Gly Lys Ser Val Gly Ile Met Leu Thr Glu Leu Glu Lys Ala
20 25 30
Leu Asn Ser Ile Ile Asp Val Tyr His Lys Tyr Ser Leu Ile Lys Gly
35 40 45
Asn Phe His Ala Val Tyr Arg Asp Asp Leu Lys Lys Leu Leu Glu Thr
50 55 60
Glu Cys Pro Gln Tyr Ile Arg Lys Lys Gly Ala Asp Val Trp Phe Lys
65 70 75 80
Glu Leu Asp Ile Asn Thr Asp Gly Ala Val Asn Phe Gln Glu Phe Leu
85 90 95
Ile Leu Val Ile Lys Met Gly Val Ala Ala His Lys Lys Ser His Glu
100 105 110
Glu Ser His Lys Glu
115
<210> 11
<211> 116
<212> PRT
<213> Homo sapiens
<400> 11
Met Ser Leu Val Ser Cys Leu Ser Glu Asp Leu Val Leu Phe Phe Arg
1 5 10 15
Trp Gly Lys Ser Val Gly Ile Met Leu Thr Glu Leu Glu Lys Ala Leu
20 25 30
Asn Ser Ile Ile Asp Val Tyr His Lys Tyr Ser Leu Ile Lys Gly Asn
35 40 45
Phe His Ala Val Tyr Arg Asp Asp Leu Lys Lys Leu Leu Glu Thr Glu
50 55 60
Cys Pro Gln Tyr Ile Arg Lys Lys Gly Ala Asp Val Trp Phe Lys Glu
65 70 75 80
Leu Asp Ile Asn Thr Asp Gly Ala Val Asn Phe Gln Glu Phe Leu Ile
85 90 95
Leu Val Ile Lys Met Gly Val Ala Ala His Lys Lys Ser His Glu Glu
100 105 110
Ser His Lys Glu
115
<210> 12
<211> 101
<212> PRT
<213> Homo sapiens
<400> 12
Met Trp Gly Lys Ser Val Gly Ile Met Leu Thr Glu Leu Glu Lys Ala
1 5 10 15
Leu Asn Ser Ile Ile Asp Val Tyr His Lys Tyr Ser Leu Ile Lys Gly
20 25 30
Asn Phe His Ala Val Tyr Arg Asp Asp Leu Lys Lys Leu Leu Glu Thr
35 40 45
Glu Cys Pro Gln Tyr Ile Arg Lys Lys Gly Ala Asp Val Trp Phe Lys
50 55 60
Glu Leu Asp Ile Asn Thr Asp Gly Ala Val Asn Phe Gln Glu Phe Leu
65 70 75 80
Ile Leu Val Ile Lys Met Gly Val Ala Ala His Lys Lys Ser His Glu
85 90 95
Glu Ser His Lys Glu
100
<210> 13
<211> 93
<212> PRT
<213> Homo sapiens
<400> 13
Met Leu Thr Glu Leu Glu Lys Ala Leu Asn Ser Ile Ile Asp Val Tyr
1 5 10 15
His Lys Tyr Ser Leu Ile Lys Gly Asn Phe His Ala Val Tyr Arg Asp
20 25 30
Asp Leu Lys Lys Leu Leu Glu Thr Glu Cys Pro Gln Tyr Ile Arg Lys
35 40 45
Lys Gly Ala Asp Val Trp Phe Lys Glu Leu Asp Ile Asn Thr Asp Gly
50 55 60
Ala Val Asn Phe Gln Glu Phe Leu Ile Leu Val Ile Lys Met Gly Val
65 70 75 80
Ala Ala His Lys Lys Ser His Glu Glu Ser His Lys Glu
85 90
<210> 14
<211> 114
<212> PRT
<213> Homo sapiens
<400> 14
Met Thr Cys Lys Met Ser Gln Leu Glu Arg Asn Ile Glu Thr Ile Ile
1 5 10 15
Asn Thr Phe His Gln Tyr Ser Val Lys Leu Gly His Pro Asp Thr Leu
20 25 30
Asn Gln Gly Glu Phe Lys Glu Leu Val Arg Lys Asp Leu Gln Asn Phe
35 40 45
Leu Lys Lys Glu Asn Lys Asn Glu Lys Val Ile Glu His Ile Met Glu
50 55 60
Asp Leu Asp Thr Asn Ala Asp Lys Gln Leu Ser Phe Glu Glu Phe Ile
65 70 75 80
Met Leu Met Ala Arg Leu Thr Trp Ala Ser His Glu Lys Met His Glu
85 90 95
Gly Asp Glu Gly Pro Gly His His His Lys Pro Gly Leu Gly Glu Gly
100 105 110
Thr Pro
<210> 15
<211> 323
<212> PRT
<213> Homo sapiens
<400> 15
Met Ala Arg Gly Pro Gly Leu Ala Pro Pro Pro Leu Arg Leu Pro Leu
1 5 10 15
Leu Leu Leu Val Leu Ala Ala Val Thr Gly His Thr Ala Ala Gln Asp
20 25 30
Asn Cys Thr Cys Pro Thr Asn Lys Met Thr Val Cys Ser Pro Asp Gly
35 40 45
Pro Gly Gly Arg Cys Gln Cys Arg Ala Leu Gly Ser Gly Met Ala Val
50 55 60
Asp Cys Ser Thr Leu Thr Ser Lys Cys Leu Leu Leu Lys Ala Arg Met
65 70 75 80
Ser Ala Pro Lys Asn Ala Arg Thr Leu Val Arg Pro Ser Glu His Ala
85 90 95
Leu Val Asp Asn Asp Gly Leu Tyr Asp Pro Asp Cys Asp Pro Glu Gly
100 105 110
Arg Phe Lys Ala Arg Gln Cys Asn Gln Thr Ser Val Cys Trp Cys Val
115 120 125
Asn Ser Val Gly Val Arg Arg Thr Asp Lys Gly Asp Leu Ser Leu Arg
130 135 140
Cys Asp Glu Leu Val Arg Thr His His Ile Leu Ile Asp Leu Arg His
145 150 155 160
Arg Pro Thr Ala Gly Ala Phe Asn His Ser Asp Leu Asp Ala Glu Leu
165 170 175
Arg Arg Leu Phe Arg Glu Arg Tyr Arg Leu His Pro Lys Phe Val Ala
180 185 190
Ala Val His Tyr Glu Gln Pro Thr Ile Gln Ile Glu Leu Arg Gln Asn
195 200 205
Thr Ser Gln Lys Ala Ala Gly Asp Val Asp Ile Gly Asp Ala Ala Tyr
210 215 220
Tyr Phe Glu Arg Asp Ile Lys Gly Glu Ser Leu Phe Gln Gly Arg Gly
225 230 235 240
Gly Leu Asp Leu Arg Val Arg Gly Glu Pro Leu Gln Val Glu Arg Thr
245 250 255
Leu Ile Tyr Tyr Leu Asp Glu Ile Pro Pro Lys Phe Ser Met Lys Arg
260 265 270
Leu Thr Ala Gly Leu Ile Ala Val Ile Val Val Val Val Val Ala Leu
275 280 285
Val Ala Gly Met Ala Val Leu Val Ile Thr Asn Arg Arg Lys Ser Gly
290 295 300
Lys Tyr Lys Lys Val Glu Ile Lys Glu Leu Gly Glu Leu Arg Lys Glu
305 310 315 320
Pro Ser Leu

Claims (8)

1.组合基因在制备诊断食管鳞癌的产品中的应用，其特征在于，所述组合基因包括如下基因：CCL20基因，GSTP1基因，HSPB1基因，KRT14基因，KRT15基因，S100A8基因，S100A9基因，TACSTD2基因。
2.根据权利要求1所述的应用，其特征在于，所述产品可与下列任意一种检测方式相结合来诊断食管鳞癌：RT-PCR、实时定量PCR、免疫检测、原位杂交、芯片检测、高通量测序平台检测。
3.根据权利要求1所述的应用，其特征在于，所述产品包括检测样本中CCL20基因表达的蛋白、GSTP1基因表达的蛋白、HSPB1基因表达的蛋白、KRT14基因表达的蛋白、KRT15基因表达的蛋白、S100A8基因表达的蛋白、S100A9基因表达的蛋白、TACSTD2基因表达的蛋白的试剂。
4.根据权利要求1所述的应用，其特征在于，所述产品包括芯片或试剂盒；其中，所述芯片包括基因芯片、蛋白质芯片；所述试剂盒包括基因检测试剂盒、蛋白免疫检测试剂盒。
5.权利要求1所述的组合基因在制备治疗食管鳞癌的药物组合物中的应用。
6.根据权利要求5所述的应用，其特征在于，所述药物组合物包括增加组合基因表达、增强组合基因表达功能、和/或增强组合基因表达产物活性的试剂。
7.根据权利要求6所述的应用，其特征在于，所述试剂包括：含有能编码功能性组合基因分泌蛋白的核酸的试剂、组合基因分泌蛋白的激活剂、含有组合基因分泌蛋白质的试剂。
8.根据权利要求5所述的应用，其特征在于，所述药物组合物还包括药学上可接受的载体。
CN202011048576.7A 2020-09-29 2020-09-29 组合基因在食管鳞癌中的应用 Pending CN112210603A (zh)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114381527A (zh) * 2022-01-29 2022-04-22 中山大学孙逸仙纪念医院 一种食管癌免疫治疗预后的新型生物标记物及应用

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CN114381527A (zh) * 2022-01-29 2022-04-22 中山大学孙逸仙纪念医院 一种食管癌免疫治疗预后的新型生物标记物及应用
CN114381527B (zh) * 2022-01-29 2022-08-02 中山大学孙逸仙纪念医院 一种食管癌免疫治疗预后的新型生物标记物及应用

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