CN114959028B - 一种snoRNA生物标志物的应用及相关试剂盒 - Google Patents
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Abstract
一种snoRNA生物标志物的应用及相关试剂盒,属于生物医药技术领域。为了探索snoRNAs在CRC中的生物学功能和机制,进而为CRC诊断和治疗提供新的思路,本发明通过对SNORD15B和SNORA5C这两个基因在CRC组织和邻近正常组织中表达量进行分析,发现SNORD15B和SNORA5C这两个基因在CRC组织和邻近正常组织中的差异表达,并通过体外实验证实它们对CRC细胞增殖和克隆形成具有促进作用。通过临床队列分析,发现SNORD15B和SNORA5C高表达与CRC患者临床预后负相关。本研究数据表明,SNORD15B和SNORA5C是CRC发病过程中发挥促癌作用的snoRNA分子,是潜在的CRC诊断和预后标志物。
Description
技术领域
本发明属于生物医药技术领域,具体涉及一种snoRNA生物标志物的应用及相关试剂盒。
背景技术
结直肠癌(CRC)是一种常见的恶性肿瘤,最常发生在直肠和乙状结肠,目前已成为世界范围内严重的公共卫生问题。根据WHO的2020年全球癌症数据,全球新增194万CRC病例,其中有94万死亡病例,其发病率和死亡率均居第二位。流行病学研究表明,CRC的发病机制受到多种因素的影响,如遗传、年龄、生活方式、环境、肠道微生物组和慢性炎症等。在CRC的早期阶段,难以观察到明显的临床症状,但随着疾病的发展,会出现诸如肠道习惯改变、便血、腹泻和腹痛等表现。在CRC的晚期,会出现贫血和体重下降等全身性消耗症状。在早期阶段诊断CRC是消除肿瘤或延长患者生存时间的关键步骤。目前,粪便隐血试验(FOBT)和结肠镜检查仍然是早期大肠癌诊断的最重要方法(E.Dekker,P.J.Tanis,J.L.A.Vleugels,P.M.Kasi,M.B.Wallace,Colorectal cancer,Lancet(London,England)394(2019)1467-1480.10.1016/s0140-6736(19)32319-0.)。因此,迫切需要更有效的方法来进行CRC的早期诊断或预后预测。
非编码RNAs(ncRNAs)是一类无明显开放阅读框、蛋白质编码能力很弱或无编码能力的RNA分子,占人类基因组转录产物的90%以上,在生物体内发挥多种生物学功能。核仁小RNA(Small nucleolar RNAs,snoRNAs是小的ncRNAs,长度约为60-300个核苷酸,主要位于核小体中。在脊椎动物(如人类)中,snoRNAs大多由宿主基因(编码或非编码基因)内含子区域的可变剪接衍生而来。根据snoRNAs分子中不同的保守结构域,主要分为两类:C/D盒snoRNA和H/ACA盒snoRNA。snoRNAs的主要功能是指导rRNA或snRNA转录后修饰,C/D盒snoRNAs主要参与2'-O-甲基化,而H/ACA盒snoRNAs主要参与假酸化。
近几年研究表明,snoRNAs可以在多个层面调控肿瘤疾病过程,而不仅仅是曾经认为的那样充当"管家基因"。随着研究证据的积累,snoRNAs在肿瘤诊断、预后评估和靶向治疗方面显示出良好的前景,使snoRNAs相关的生物学功能研究成为肿瘤学领域的新热点。研究人员发现,snoRNAs在黑色素瘤、卵巢癌、肝癌、肺癌、乳腺癌等恶性肿瘤及其他疾病中均存在异常表达(T.J.B.Rogelj,Functional diversity of smallnucleolar RNAs,Nucleic acids research 48(2020)1627-1651.10.1093/nar/gkz1140.)(G.Romano,D.Veneziano,M.Acunzo,C.M.Croce,Small non-coding RNA and cancer,Carcinogenesis 38(2017)485-491.10.1093/carcin/bgx026.)。最近的研究表明,snoRNAs在CRC疾病过程中的作用应受到重视。如SNORA21和SNORA42过量表达会促进CRC细胞的增殖、迁移和侵袭,也会增强肿瘤的发生率,其上调表达会导致患者生存率下降(Y.Okugawa,Y.Toiyama,S.Toden,H.Mitoma,T.Nagasaka,K.Tanaka,Y.Inoue,M.Kusunoki,C.R.Boland,A.Goel,Clinical significance of SNORA42 as an oncogene and a prognosticbiomarker in colorectal cancer,Gut 66(2017)107-117.10.1136/gutjnl-2015-309359.)(K.Yoshida,S.Toden,W.Weng,K.Shigeyasu,J.Miyoshi,J.Turner,T.Nagasaka,Y.Ma,T.Takayama,T.Fujiwara,A.Goel,SNORA21-An Oncogenic Small Nucleolar RNA,with a Prognostic Biomarker Potential in Human Colorectal Cancer,EBioMedicine22(2017)68-77.10.1016/j.ebiom.2017.07.009.)。此外,snoRNAs宿主基因(如SNHG1、SNHG6和SNHG11)通常与位于其序列中的snoRNAs共同表达,在CRC组织中会出现表达紊乱。这些snoRNA宿主基因对CRC生长、迁移和侵袭有明显影响,并与CRC患者的不良预后密切相关。但是,多数snoRNAs与其宿主基因之间的功能联系仍不明确。目前研究表明,snoRNAs在肿瘤的发生、发展中起着至关重要的作用,因此探索snoRNAs在CRC中的生物学功能和机制能为改善CRC诊断和治疗提供新的思路。
发明内容
为了探索snoRNAs在CRC中的生物学功能和机制,进而为CRC诊断和治疗提供新的思路,本发明提供了一种snoRNA生物标志物在制备结直肠癌检测试剂盒中的应用,所述snoRNA生物标志物为核苷酸序列如SEQ ID NO.1所示的SNORD15B基因或核苷酸序列如SEQID NO.2所示的SNORA5C基因。
进一步地限定,所述试剂盒用于结直肠癌诊断和/或预后评估;与正常癌旁组织相比,所述SNORD15B基因或SNORA5C基因在结直肠癌细胞或组织中高表达。
本发明还提供了扩增上述SNORD15B基因的引物在制备结直肠癌检测试剂盒中的应用。
进一步地限定,所述试剂盒用于结直肠癌诊断和/或预后评估;与正常癌旁组织相比,所述SNORD15B基因在结直肠癌细胞或组织中高表达。
进一步地限定,所述引物的序列为:
正向:5'-GTCACGTCCTGCTCTTGGTC-3';
反向:5'-CACTTCTGCCAAAGGAACTCG-3'。
本发明还提供了扩增上述SNORA5C基因的引物在制备结直肠癌检测试剂盒中的应用。
进一步地限定,所述试剂盒用于结直肠癌诊断和/或预后评估;与正常癌旁组织相比,所述SNORA5C基因在结直肠癌细胞或组织中高表达。
进一步地限定,所述引物的序列为:
正向:5'-TTCAGTGCCCGTTTCTGTCATA-3';
反向:5'-CAAACTTATCCCCAGGTCCCAG-3'。
本发明还提供了一种结直肠癌诊断试剂盒,所述试剂盒包括上述的SNORD15B基因或SNORA5C基因或上述两种引物中的任意一种。
本发明还提供了一种结直肠癌预后评估试剂盒,所述试剂盒包括上述的SNORD15B基因或SNORA5C基因或上述两种引物中的任意一种。
本发明的有益效果:
本发明发现SNORD15B、SNORD48和SNORA5C在临床CRC组织中的表达水平高于邻近的正常粘膜组织,对CRC癌组织与邻近的正常粘膜组织分类具有诊断意义,且SNORD15B、SNORD48和SNORA5C高水平表达与CRC以及其多种癌症不良预后相关。进一步地研究发现体外实验中,高水平表达SNORD15B和SNORA5C(SNORD48除外)促进了CRC细胞的增殖和克隆形成。同时,通过对基因表达水平和CRC临床病理参数的相关分析,我们发现SNORD15B和SNORA5C参与了CRC的肿瘤发生和转移,并成为导致总生存率下降的独立危险因素。
本发明发现SNORD15B和SNORA5C是CRC发病过程中发挥促癌作用的snoRNA分子,是潜在的CRC早期诊断和预后评估标志物。
附图说明
图1为41位患者的临床病理学特征详细信息;
图2为SNORD15B、SNORD48和SNORA5C在结直肠癌组织中的表达水平;其中,图2中的A为三对结直肠癌组织中SNORD15B、SNORD48和SNORA5C的表达水平,图2中的B、C和D分别为SNORD15B、SNORD48和SNORA5C在CRC组织中与相邻的正常粘膜组织中的表达情况(P<0.001),图2中的E、F和G分别为SNORD15B、SNORD48和SNORA5C在结直肠癌和正常黏膜组织中表达情况的ROC曲线分析结果图;
图3为SNORD15B、SNORD48和SNORA5C在多种恶性肿瘤中的表达情况;
图4为SNORD15B、SNORD48和SNORA5C三个基因表达水平与COAD患者5年总生存的关系;
图5为SNORD15B、SNORD48和SNORA5C的表达对各种癌症患者5年生存率的影响结果图;
图6为不同结直肠上皮细胞中SNORD15B、SNORD48和SNORA5C的表达水平;
图7为慢病毒感染HT29细胞中SNORD15B、SNORD48和SNORA5C表达对细胞增殖及克隆形成的影响;其中,图7中的A、B和C分别为SNORD15B、SNORD48和SNORA5C在慢病毒感染的HT29细胞中的表达水平,图7中的D、E和F分别为SNORD15B、SNORD48和SNORA5C对HT29细胞增殖的影响,图7中的G、H、I、J、K和L为三个基因对HT29克隆形成的影响;
图8为慢病毒感染HCT116细胞中SNORD15B、SNORD48、SNORA5C表达对细胞增殖及克隆形成的影响;其中,图8中的A、B和C分别为SNORD15B、SNORD48和SNORA5C在慢病毒感染HCT116细胞中的表达水平,图8中的D、E和F分别为SNORD15B、SNORD48和SNORA5C对HCT116细胞增殖的影响,图8中的G、H、I、J、K和L为三个基因对HT29克隆形成的影响;
图9为由SNORD15B和SNORA5C这两个基因组成的小组对CRC患者5年总生存的影响结果图。
具体实施方式
实施例1:SNORD15B基因和SNORA5C基因与结肠癌病理参数相关性的研究。
一、患者及组织标本
本发明分析了41名患者的新鲜冷冻CRC肿瘤组织和邻近正常粘膜组织标本。组织来自于辽宁省肿瘤医院(中国)。本发明的研究内容得到了辽宁省肿瘤医院伦理委员会的批准,并征得了每个患者的知情同意。患者临床病理学特征的详细信息见图1。
二、细胞培养
HCT116、SW620和HT29细胞系购自GeneChem(中国上海),人类正常结肠上皮细胞(FHC)细胞系购自美国ATCC公司(Manassas,Virginia)。HCT116和SW620细胞系在RPMI-1640培养基中培养,HT29细胞系在Dulbecco'sModifiedEagleMedium(HyClone)中培养,这两种培养基都补充了10%的胎牛血清(ExCellBio,中国)。FHC在DMEM中培养:F-12(ATCC,30-2006),在基础培养基中加入以下成分:额外的10mM HEPES(最终浓度为25mM),10ng/mL霍乱毒素,0.005mg/mL胰岛素,0.005mg/mL转铁蛋白,100ng/mL氢化可的松,20ng/mL人重组EGF(Thermo Fisher PHG0311),胎牛血清,10%最终浓度(GIBCO),此外,在所有培养基中添加1%青霉素-链霉素(HyClone,美国)。所有的细胞都在37℃、含有5%二氧化碳的湿润气氛中培养。
三、RNA提取和qRT-PCR
在每个样品中加入1mL TRIzol试剂(Ambion,美国),根据制造商的说明提取总RNA。使用PrimeSript RT试剂盒(Takara,日本)将1μg总RNA逆转录为cDNA。使用iTaqUniversal SYBR Green Supermix(BioRad,美国)进行qRT-PCR,检测snoRNA表达水平。在qRT-PCR数据分析中,U6为内参基因,目标基因的相对表达量用2-ΔΔCt公式计算。为了保证定量的准确性,每个样品都设置了三个重复。使用的引物序列见表1。
表1引物序列信息
四、慢病毒感染
表达SNORD15B(LV-SNORD15B)、SNORA5C(LV-SNORA5C)、SNORD48(LV-SNORD48)或阴性对照寡核苷酸序列(LV-NC)的慢病毒由上海吉凯基因医药科技有限公司构建。本研究中使用的snoRNAs和NC的序列如下:
SNORD15B(SEQ ID NO.1):
5'-cttcagtgatgacacgatgacgagtcagaaaggtcacgtcctgctcttggtccttgtcagtgccatgttctgtggtgctgtgcacgagttcctttggcagaagtgtcctatttattgatcgatttagaggcatttgtctgagaagg-3';
SNORA5C(SEQ ID NO.2):
5'-TGCAGTCAAGTCAAATTCAGTGCCCGTTTCTGTCATAGCGGGGGCTGGCCCAGATGGCTGCCACAGCAAGCTCCACAGCTCATGGGCCCTGGGTCACCTACCCTGGGACCTGGGGATAAGTTTGGCTGTGGACAGTG-3';
SNORD48(SEQ ID NO.11):
5'-AGTGATGATGACCCCAGGTAACTCTGAGTGTGTCGCTGATGCCATCACCGCAGCGCTCTGACC-3';
NC(SEQ ID NO.12):
5'-TTCTCCGAACGTGTCACGT-3'。
将HCT116或HT29细胞接种至12孔板(15000个细胞/孔)培养24小时,将表达目标基因或NC的慢病毒分别加入到培养基中,病毒感染浓度10MOI。感染24小时后,更换新鲜1mL培养基。感染72小时后,将细胞在含有嘌呤霉素(2μg/mL)的选择培养基中培养5天。最后,将稳定感染的细胞在含有0.67μg/mL嘌呤霉素的培养基中持续培养。
五、细胞增殖
细胞计数试剂盒-8(CCK-8)试验(Dojindo,日本)用来测试细胞的增殖能力。在96孔板的每个孔中接种两千个细胞,分别在0、1、2、3、4、5天内用酶标仪(Sunrise,Tecan,瑞士)对450nm处的吸光度进行测定,每组5次重复。
六、克隆形成实验
在6孔板的每个孔中接种1500个细胞,培养10-12天,每4天更换一次培养基。细胞在甲醇中固定30分钟,然后在室温下用Gimsa染色30分钟。每组有三个重复。
七、统计学分析
数据以平均值±标准差表示,所有实验均设置了三个或以上重复。使用Kaplan-Meier方法分析snoRNA表达水平与临床预后的关系,并绘制了生存曲线。使用Cox回归模型(coxph)评估了snoRNA表达水平与CRC患者5年生存率之间的关系。采用双尾学生t检验或双向方差分析评估对照组和实验组之间的统计学意义。统计分析和绘图使用SPSS软件24.0版和GraphPadPrism7.0版进行。P<0.05被认为有统计学意义,ns表示无意义。
八、生物信息学网站
CRC患者临床数据从The Cancer Gneome Atlas(TCGA)下载(网站:https://portal.gdc.cancer.gov/)。SnoRNAs表达谱从SnoRNA in Cancers(SNORic)下载(参见文献:J.Gong,Y.Li,C.-j.Liu,Y.Xiang,C.Li,Y.Ye,Z.Zhang,D.H.Hawke,P.K.Park,L.Diao,J.A.Putkey,L.Yang,A.-Y.Guo,C.Lin,L.Han,A Pan-cancer Analysis of theExpression and Clinical Relevance of Small Nucleolar RNAs in Human Cancer,Cell Reports 21(2017)1968-1981.10.1016/j.celrep.2017.10.070.),不同类型肿瘤的总生存分析数据也从SNORic获得。
结果与分析:
一、SNORD15B、SNORD48和SNORA5C在CRC组织中表达上调
为了探索snoRNAs在CRC疾病过程中潜在的生物学功能,我们采用RNA-seq技术对三对CRC和邻近的正常粘膜组织对异常表达的snoRNAs进行了筛选。发现在癌症组织中有一部分snoRNAs表达失调。我们注意到,SNORD15B、SNORD48和SNORA5C等snoRNA基因的表达在CRC组织中与邻近的正常粘膜组织相比明显上调(见图2中的A)。随后,为了验证这三个基因在CRC患者的癌组织和邻近的正常粘膜组织中的表达是否有差异,用qRT-PCR检测了41对CRC癌与癌旁组织中上述基因表达水平。结果显示,SNORD15B、SNORD48和SNORA5C在癌组织中的表达水平明显高于癌旁组织(见图2中的B、C和D)。接受者操作特征(ROC)曲线分析表明,这三个基因的表达成功地将CRC与邻近的正常粘膜组织区分开来(曲线下面积:SNORD15B0.8294,SNORD480.6917,SNORA5C0.8615;95%置信区间:SNORD15B0.7408-0.9180,SNORD480.5722-0.8113,SNORA5C0.7734-0.9496;SNORD15BP<0.0001,SNORD48P=0.0046,SNORA5CP<0.0001)(见图2中的E、F和G)。除此之外,令人惊讶的是,根据SNORic的数据,这些基因在多种恶性肿瘤中都是上调的(见图3)。这些结果表明,三个上调的snoRNASNORD15B、SNORD48和SNORA5C的表达水平可能是CRC或其他一些癌症的潜在生物诊断标志物。
二、SNORD15B、SNORD48和SNORA5C等基因高表达与CRC患者的预后不良相关
这些snoRNAs的异常表达与CRC患者临床预后之间是否有关联?为了探索这个问题,我们在SNORic数据库中检索SNORD15B、SNORD48和SNORA5C,通过Cox风险回归模型(coxph)分析了这三个基因表达与COAD患者5年总生存的关系,发现SNORD15B、SNORD48和SNORA5C高表达都导致结肠腺癌(COAD)患者的五年总生存率下降(见图4)。除此以外,使用Kaplan-Meier法绘制癌症患者总生存期的生存曲线,以SNORD15B、SNORD48和SNORA5C的中位表达量作为截止点,得到SNORD15B、SNORD48和SNORA5C的表达对各种癌症患者5年生存率的影响(见图5),该图表明,SNORD15B和SNORA5C表达水平升高与多种癌症的不良预后相关,包括食道癌(ESCA)、肾上腺皮质癌(ACC)、肉瘤(SARC)、肾脏肾透明细胞癌(KIRC)和甲状腺癌(THCA)。而SNORD48在宫颈鳞状细胞癌和宫颈内膜腺癌(CESC)、肺腺癌(LUAD)和子宫冠状内膜癌(UCEC)中的水平似乎是一个保护因素。这些发现表明,SNORD15B、SNORD48和SNORA5C高表达可能是CRC(包括COAD)的潜在危险因素,它们和肿瘤预后的生物学效应与组织类型有一定的关系。
三、SNORD15B和SNORA5C对CRC细胞的增殖和集落形成有积极影响
为了进一步验证SNORD15B、SNORD48和SNORA5C在CRC中的作用,我们首先检测了人类CRC细胞(HT29、HCT116和SW620)和正常结直肠上皮细胞FHC中目标基因的表达。数据显示,这三个snoRNAs在CRC细胞中的表达水平并不总是高于正常结直肠癌上皮细胞(见图6)。本发明采用HT29和HCT116细胞进行增殖和克隆形成分析。用过表达目标基因的慢病毒或对照病毒感染细胞后,用RT-qPCR检测目标基因的水平,用CCK-8增殖试验测量两个细胞系的细胞活力。首先,在慢病毒感染的细胞中验证了SNORD15B、SNORD48和SNORA5C的表达水平(图7中的A、B和C,图8中的A、B和C)。增殖分析结果显示,SNORD15B和SNORA5C促进HT29和HCT116细胞的增殖。然而,SNORD48对细胞增殖无明显影响(图7中的D、E和F,图8中的D、E和F)。同时,SNORD15B和SNORA5C也增强了细胞的克隆形成能力,而LV-SNORD48和对照组细胞克隆形成率没有明显的差异(图7中的G、H和L,图8中的G、H和L)。上述结果表明SNORD15B和SNORA5C在CRC病理过程中可能通过促进癌细胞增殖和存活发挥促癌作用。
四、高水平的SNORD15B和SNORA5C与CRC的肿瘤发生和转移有关
为了了解SNORD15B和SNORA5C在CRC进展中的作用,根据从TCGA下载的数据,通过卡方检验分析了SNORD15B和SNORA5C的表达水平与CRC患者的临床病理参数之间的相关性。根据所有患者的基因表达的截止阈值(中位值),将CRC队列分为2组。我们评估了SNORD15B和SNORA5C表达水平与临床CRC患者病理特征(性别、年龄、TNM分期、淋巴结侵犯、静脉侵犯、结肠息肉史和生存时间等)之间的关系。如表2所示,SNORD15B的表达与高龄(>70岁)(P=0.003,χ=9.076)、淋巴转移(P=0.048,χ=3.901)和结肠息肉史(P<0.001,χ=17.532)明显相关。同样在表3中,SNORA5C的表达与年龄、淋巴侵犯和结肠息肉病史明显相关:高龄(P=0.041,χ=4.174)、淋巴转移(P<0.001,χ=12.681)和结肠息肉(P=0.002,χ=9.443)病史。众所周知,高龄和结肠息肉史是CRC发生的重要危险因素。而肿瘤细胞侵犯淋巴结和发生远端转移会极大地促进CRC恶性进展,从而导致患者临床预后不良。我们的研究结果表明,SNORD15B和SNORA5C可能在CRC发生和转移的病理过程中具有致癌功能。
表2 SNORD15B表达与临床病理参数之间的关系
注:SNORD15B表达的截止阈值是本队列中所有患者的中值;*p<0.05。
表3 SNORA5C表达与临床病理参数之间的关系
注:SNORD15B表达的截止阈值是本队列中所有患者的中值;*p<0.05。
五、SNORD15B和SNORA5C表达水平是抑制CRC预后的独立危险因素
为了进一步明确SNORD15B和SNORA5C对患者预后的影响,我们应用单变量和多变量COX回归模型来分析影响CRC患者总生存的临床因素(表4和表5)。在单变量因素分析中显示,年龄、TNM分期、淋巴结转移、静脉浸润和SNORD15B高水平与总生存期显著相关;而在多变量分析中,年龄、TNM分期和SNORD15B表达水平被证实是CRC生存期的独立预后风险因素(表4)。对于SNORA5C,情况与SNORD15B类似(表5)。所有这些结果表明,在CRC患者中,SNORD15B和SNORA5C的高表达水平可以预测不良的预后。那么这两个基因的高水平是否会导致更坏的结果呢?如前所述,我们组建了一个由这两个基因组成的小组来分析其对CRC5年总生存的影响。如我们的数据所示,这两个基因对CRC患者的总生存率没有协同作用(高组生存率为53%,低组为63%)(图9)。所有这些证据证明,SNORD15B和SNORA5C在CRC组织中的高表达是影响患者不良预后的独立危险因素。
表4SNORD15B与结直肠癌总生存期的Cox回归分析
注:SNORD15B表达的临界值是本队列所有患者的中值;*P<0.05。
表5SNORA5C与结直肠癌总生存期的Cox回归分析
注:SNORA5C表达的临界值是本队列所有患者的中值;*P<0.05。
综上所述,我们的研究表明,SNORD15B、SNORD48和SNORA5C在CRC组织中呈上调表达。其中,SNORD15B和SNORA5C对CRC细胞的增殖和集落形成有积极作用。它们的高水平与CRC的癌变和转移有关,并能独立预测患者的不良预后,为CRC的诊断和预后预测提供了新的潜在生物标志物。
虽然本发明已以较佳的实施例公开如上,但其并非用以限定本发明,任何熟悉此技术的人,在不脱离本发明精神和范围内,都可以做各种的改动与修饰,因此,本发明的保护范围应该以权利要求书所界定的为准。
Claims (8)
1.一种检测snoRNA生物标志物的试剂在制备结直肠癌检测试剂盒中的应用,所述snoRNA生物标志物为核苷酸序列如SEQ ID NO.1所示的SNORD15B基因或核苷酸序列如SEQID NO.2所示的SNORA5C基因。
2.根据权利要求1所述的应用,其特征在于,所述试剂盒用于结直肠癌诊断和/或预后评估;与正常癌旁组织相比,所述SNORD15B基因或SNORA5C基因在结直肠癌细胞或组织中高表达。
3.扩增权利要求1所述SNORD15B基因的引物在制备结直肠癌检测试剂盒中的应用。
4.根据权利要求3所述的应用,其特征在于,所述试剂盒用于结直肠癌诊断和/或预后评估;与正常癌旁组织相比,所述SNORD15B基因在结直肠癌细胞或组织中高表达。
5.根据权利要求3所述的应用,其特征在于,所述引物的序列为:
正向:5'-GTCACGTCCTGCTCTTGGTC-3';
反向:5'-CACTTCTGCCAAAGGAACTCG-3'。
6.扩增权利要求1所述SNORA5C基因的引物在制备结直肠癌检测试剂盒中的应用。
7.根据权利要求6所述的应用,其特征在于,所述试剂盒用于结直肠癌诊断和/或预后评估;与正常癌旁组织相比,所述SNORA5C基因在结直肠癌细胞或组织中高表达。
8.根据权利要求6所述的应用,其特征在于,所述引物的序列为:
正向:5'-TTCAGTGCCCGTTTCTGTCATA-3';
反向:5'-CAAACTTATCCCCAGGTCCCAG-3'。
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