CN115261464A - 一组消化道泛癌诊疗用mRNA靶点 - Google Patents
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Abstract
本发明涉及一种一组消化道泛癌诊疗用mRNA靶点，公开了一种预防或治疗消化道泛癌的特异性基因靶点。具体地，本发明发现MIR22HG,hsa‑mir‑196b and hsa‑mir‑584基因在胃肠癌肿瘤的细胞增殖过程中起到重要作用。本发明的生物标志物具有作为胃肠癌标志物的潜能，精准率高，特异性强，是一组新的消化道癌肿瘤诊疗基因靶点，具有辅助消化道肿瘤癌的预测诊断，预防性治疗及预后评估作用。有益效果：提供了一组在胃肠道癌与胃肠道癌患者生存显著相关的基因，所述基因与胃肠道癌的增殖相关；所述的基因与胃肠癌之间的关系的发现对于推动胃肠癌的早期诊断和个性化治疗具有重要意义。
Description
技术领域
本发明属于生物医药领域，涉及一组消化道泛癌诊疗用mRNA靶点，具体地，本发明涉及一组预防或治疗胃肠癌的特异性基因靶点及其应用。
背景技术
消化道癌症(gastrointestinal tumors)多数患者早期无明显症状或症状不明显，随着癌肿发展，症状逐渐出现，由于缺乏早期的诊疗手段，患者发现时往往已是癌症晚期，严重威胁着人们的生命健康，随着肿瘤综合治疗的发展，胃肠道癌的治疗取得了一定的进步，但是近年来，患者的5年生存率没有明显改善。目前临床上对胃肠道癌症的治疗方法包括手术治疗、术前或术后放化疗等，但仅仅这些治疗方法还远远不能满足患者生存的需要，有一部分患者即使经过手术和辅助放化疗，但依然存在术后复发和转移的可能，严重影响患者的总体生存时间。这是因为现有病理诊断技术不能准确判断胃肠道癌症的生物学特性，缺乏特异性、高效性的针对胃肠道癌治疗药物和方案。随着分子生物技术的快速发展，与早期胃肠道癌患者预后相关的生物标志物不断被发现。本申请筛选出一种新的胃肠道癌生物标志物，用于胃肠道癌的诊断和治疗。
发明内容
要解决的技术问题
为了避免现有技术的不足之处，本发明提出一种一组消化道泛癌诊疗用mRNA靶点，弥补现有消化道癌症早期手段的不足。目的在于提供一种诊断和预防性治疗消化道癌症的生物标志物，进而为消化道癌症的诊疗提供一种分子手段，用于解决现有消化道癌症分子诊断试剂技术方法中的问题。
技术方案
本发明的第一方面提供一组胃肠癌诊断用RNA生物标志物，一种一组消化道泛癌诊疗用mRNA靶点，其特征在于：mRNA生物标志物由如下RNA组成：MIR22HG, hsa-mir-196band hsa-mir-584。
所述的mRNA生物标志物基因选自下组：
(1)MIR22HG，编码如SEQ ID NO.1所示基因序列
(2)hsa-mir-196b，编码如SEQ ID NO.2所示基因序列
(3)hsa-mir-584，编码如SEQ ID NO.3所示基因序列。
所述的基因来源于人类。
本发明第二方面提供所述RNA生物标志物在制备预防或治疗人胃肠癌诊断药物中的用途。
优选的，所述RNA生物标志物在预测胃肠癌患者预后情况中的用途。
有益效果
本发明提出的一种一组消化道泛癌诊疗用mRNA靶点，公开了一种预防或治疗消化道泛癌的特异性基因靶点。具体地，本发明发现MIR22HG,hsa-mir-196b and hsa-mir-584基因在胃肠癌肿瘤的细胞增殖过程中起到重要作用。本发明的生物标志物具有作为胃肠癌标志物的潜能，精准率高，特异性强，是一组新的消化道癌肿瘤诊疗基因靶点，具有辅助消化道肿瘤癌的预测诊断，预防性治疗及预后评估作用。
本发明的优点和有益效果如下：
1、本发明提供了一组在胃肠道癌与胃肠道癌患者生存显著相关的基因，所述基因与胃肠道癌的增殖相关；
2、本发明中所述的基因与胃肠癌之间的关系的发现对于推动胃肠癌的早期诊断和个性化治疗具有重要意义。
附图说明
图1是mRNA生物标志物构建的ROC曲线
图2是上述基因与胃肠癌患者生存回归曲线
图3是上述基因生存相关基因免疫浸润的相关性分析
具体实施方式
现结合实施例、附图对本发明作进一步描述：
下面结合具体实施例，进一步阐述本发明，仅用于解释本发明，而不能理解为对本发明的限制。本领域的普通技术人员可以理解为：在不脱离本发明的原理和宗旨的情况下可以对这些实施例进行多种变化、修改、替换和变型，本发明的范围由权利要求及其等同物限定。下列实施例中未注明具体条件的实验方法，通常按照常规条件或按照厂商所建议的条件实施检测。
本发明所用数据具有相关领域普通技术人员通常理解的含义。然而，为了更好地理解本发明，对一些定义和相关术语的解释如下：
“生物标志物”，指可以标记系统、器官、组织、细胞及亚细胞结构或功能的改变或可能发生改变的生化指标，可用于疾病诊断、判断疾病分期或评价新药新疗法在目标人群中的安全性和有效性。
在本发明优选地实施方式中，上述基因的序列如SEQ ID NO.1-3所示
表一.miRNA序列
实施例1
生存相关遗传模型预测与比较
构建ROC曲线来分析上述mRNA生物标志物区分胃肠癌病人和健康对照的诊断能力。
图2A为风险指数生存图表，横轴代表时间(单位：天)，垂直轴代表存活率，平曲线代表高存活率或生存期较长，陡峭曲线代表低存活率或较短存活率如图所示，由上述基因区分出的高低风险组表现出明显差异。
图2B为生存一年、三年和五年的ROC曲线图。横轴为假阳性率FP，纵轴为真阳性率TP，左上角图例对应不同生存期ROC曲线的AUC值。如图所示，AUC在一年、三年和五年对应值分别为0.601、0.635、0.635。上述基因在胃肠癌中后期有较强的诊断能力。
图2C分别为甲状腺癌和乳腺癌的ROC模型曲线，结果显示，上述基因仅在胃肠癌肿瘤诊断中起作用，能作为胃肠癌诊断的生物标志物。
实施例2
生存相关(Cox)曲线分析
构建Cox曲线来比较上述基因与胃肠癌病人的生存相关性。3个RNA的Cox生存分析分别如图3所示，分析所得P值均小于0.05满足差异性检验。这些结果表明，上述基因与胃肠癌病人的生存率显著相关。
实施例3
免疫细胞浸润分析
从TCGA数据库中获取胃肠癌患者免疫细胞数据样本，利用CIBERSORT工具建立免疫细胞浸润模型，如图3A所示，颜色越深的基因，表示与免疫细胞的相关系数越大。这些结果表明上述基因与胃肠道癌症的预测或治疗具有强关联性。
序列表
<110> 西北工业大学
<120> 一组消化道泛癌诊疗用mRNA靶点
<130> 2021
<141> 2022-04-22
<160> 3
<170> SIPOSequenceListing 1.0
<210> 1
<211> 4769
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<213> Homo sapiens
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atcttcaccc atcatggagc agaggtgagg agaggcagcc tgggaatatg gagaccagtg 3720
aaggaccagg cctggagagc acagggtcct acctgggcat ccagcagagg agcccctaaa 3780
ggccaggagc accccaagag gagggagggc agccagcctc cattgacggc gagcctccag 3840
ccctctccta ctttgatcac catttctctc caggctttct gcctccgaga tgtggcacca 3900
tagtgcggtg ccctgtggct tcaccgccct acttccacct ccgcccagcc tgtaatgttt 3960
atataagcag cctcaaggac caagaaccat ctgcgaaagg acacacacag gaaattcata 4020
aaagaaatct gaatggataa aaccatgaaa aaaagtatgc ttcattagta attaaagaaa 4080
ggcaaataga gctggaagca tttttccctt agcaaaccat aacagaaaaa aataagaccc 4140
aatattggca aagagactac tgaaaaaaca ttcccataca ttgcgtgtgg gagtatacat 4200
cggtgcaggc ttcctggatg acagttgggt gatatgtgtc atgtggccta aaagcctcca 4260
tgtcatttga cctacgaatt ctatctttgg gaatttatcc taagaaaata cttaaggatt 4320
tagttagtga taagatgttc atcccagcat tgcaatggag aaaaatggga agcaatggtt 4380
tggttgggaa tttattcctt ttctgctgta acgaaagttt gcaatagggg attgcttaag 4440
taaattattg tatctccatc cagatggtgg agtaccgcgc agacattaaa agtcatgtaa 4500
aagaacatct gactgaaaga aaaatgctcc ttgaatatta aaaggttgta aaaatagtgc 4560
atgttatgtg atttcaattt tgttttttaa aatatgggtg tatgcttgta tacgtagagc 4620
agataaaaaa gacggaaggc atactaaaaa atgttgagtg gttatctttg tatggtggaa 4680
caaagtcact gtaattttca tctttggttt ttctgtaatt tccaaatttt ccacattttg 4740
tatttcatat aatataattt aagagatca 4769
<210> 2
<211> 84
<212> DNA
<213> Homo sapiens
<400> 2
actggtcggt gatttaggta gtttcctgtt gttgggatcc acctttctct cgacagcacg 60
acactgcctt cattacttca gttg 84
<210> 3
<211> 97
<212> DNA
<213> Homo sapiens
<400> 3
tagggtgacc agccattatg gtttgcctgg gactgaggaa tttgctggga tatgtcagtt 60
ccaggccaac caggctggtt ggtctccctg aagcaac 97
Claims (3)
1.一种一组消化道泛癌诊疗用mRNA靶点，其特征在于mRNA生物标志物由如下RNA组成：MIR22HG,hsa-mir-196b and hsa-mir-584。
2.根据权利要求1所述一组消化道泛癌诊疗用mRNA靶点，其特征在于：所述的mRNA生物标志物基因选自下组：
(1)MIR22HG，编码如SEQ ID NO.1所示基因序列
(2)hsa-mir-196b，编码如SEQ ID NO.2所示基因序列
(3)hsa-mir-584，编码如SEQ ID NO.3所示基因序列。
3.根据权利要求1所述一组消化道泛癌诊疗用mRNA靶点，其特征在于：所述的基因来源于人类。
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