CN115418402A - 一种乳腺癌诊断和/或预后判断用mRNA标志物及应用 - Google Patents
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Abstract
本发明涉及一种乳腺癌诊断和/或预后判断用mRNA标志物及应用,属于分子生物学和疾病诊断技术领域。乳腺癌对女性健康构成了重要威胁,该疾病耐药、转移和复发的频率较高,晚期乳腺癌患者预后状况不佳,提供一种早期诊断标志物对避免乳腺癌的不良预后具有重要意义。本发明提供了PRSS22作为乳腺癌诊断和/或预后判断用标志物的应用,该标志物在病灶组织和癌旁组织中表达量具有明显的差异,并且与乳腺癌的不良预后相关,对于乳腺癌的临床诊断及不良预后防治具有重要的检测价值。
Description
技术领域
本公开属于分子生物学和疾病诊断技术领域,具体涉及一种乳腺癌诊断和/或预后判断用mRNA标志物及应用。
背景技术
乳腺癌是世界上常见的恶性肿瘤之一,已成为女性癌症死亡的主要原因。乳腺癌转移是导致患者临床治疗失败的重要原因,严重威胁着患者的生命。寻找乳腺癌诊断和预后的标志物有利于早期发现疾病,并筛选可能预后不良的高危人群,制定疾病的临床诊疗策略,为乳腺癌的治疗提供新的思路。
PRSS22全称称为类胰蛋白酶ε和丝氨酸蛋白酶S1家族成员22,而丝氨酸蛋白酶最初被发现在胚胎发育、免疫、凝血、受精、纤维蛋白溶解、激素激活、食物消化及其他生物过程中起重要作用。近年来,其在肿瘤中的表达及作用逐渐引起了研究者的重视。虽然PRSS22已被证明在多种恶性肿瘤如胶质瘤、胰腺癌、前列腺癌、卵巢癌中存在表达,但其在乳腺癌中的表达情况及预后价值尚不清楚。
发明内容
针对上述研究背景,本领域内虽然PRSS22已被证明在多种恶性肿瘤如胶质瘤、胰腺癌、前列腺癌、卵巢癌中存在表达,但其在乳腺癌中的表达情况及预后价值尚不清楚。发明人对PRSS22与乳腺癌之间的作用关系进行了研究,研究结果表明PRSS22的表达含量与乳腺癌患者的预后情况存在相关性,有望作为乳腺癌预后判断及治疗的新型标志物。
为了实现上述目的,本发明的技术方案为:
本发明的第一方面,一种乳腺癌诊断和/或预后判断用mRNA标志物,所述mRNA标志物为PRSS22。
所述标志物选自受试者乳腺癌组织。
本发明通过研究发现PRSS22在乳腺癌中表达上调,PRSS22高表达的患者较低表达的患者预后不良,PRSS22是独立预后因子。
本发明的第二方面,检测上述标志物的物质在制备乳腺癌诊断和/或预后产品中的应用。
检测上述标志物的物质可以是采用诸如ELISA、胶体金试纸条、蛋白芯片等现有检测待测样本中相关蛋白及多肽表达情况的物质。
所述待测样本为人源样本;更具体的,所述待测样本为乳腺癌组织。
本发明的第三方面,一种用于乳腺癌诊断和/或预后判断的系统,所述系统包括∶
i)分析单元,所述分析单元包含∶用于确定受试者的待测样品中选自上述标志物表达水平的检测物质,以及;
ii)评估单元,所述评估单元包含∶根据i)中确定的所述标志物表达水平判断所述受试者患病情况;
所述待测样品包括受试者的乳腺癌病灶;
所述标志物为PRSS22。
所述评估单元中,根据乳腺癌病灶中的PRSS22的表达情况,判断受试者是否患有乳腺癌诊断和/或判断受试者乳腺癌预后情况。
所述受试者乳腺癌预后情况包括但不限于受试者生存率。
本发明的第四方面,一种诊断或辅助诊断乳腺癌的方法,所述方法包括∶
a)从受试者分离待测样品;
b)在所述受试者的待测样品中检测上述标志物的表达水平并判断所述受试者患病情况。
所述待测样品包括受试者的乳腺腺体。
所述标志物为PRSS22。
本发明的第五方面,一种乳腺癌患者预后情况判断方法所述判断方法包括检测患者病灶组织中PRSS22的含量。
本发明的有益效果为:
上述技术方案提供一种乳腺癌诊断和/或预后判断用mRNA标志物及应用。上述技术方案通过研究发现,PRSS22在乳腺癌患者的乳腺组织中表达上调,PRSS22高表达的患者较低表达的患者预后不良,PRSS22是独立预后因子。PRSS22以作为乳腺癌潜在的诊断和/或预后判断用标记物,因此具有良好的实际应用之价值。
附图说明
构成本发明的一部分的说明书附图用来提供对本发明的进一步理解,本发明的示意性实施例及其说明用于解释本发明,并不构成对本发明的不当限定。
图1为本发明实施例中PRSS22 mRNA在乳腺癌组织及正常乳腺组织中的表达情况中GEPIA数据;
图2为本发明实施例中PRSS22 mRNA在乳腺癌组织及正常乳腺组织中的表达情况中UALCAN数据;
图3为本发明实施例中PRSS22与乳腺癌患者预后不良相关情况中Kaplan Meierplotter数据;
其中,A为乳腺癌患者PRSS22表达量高低与总生存时间关系图,B为乳腺癌患者PRSS22表达量高低与无远处转移生存时间关系图,C为乳腺癌患者PRSS22表达量高低与复发后生存时间关系图;
图4为本发明实施例中PRSS22与乳腺癌患者预后不良相关情况中GOBO数据;
其中,A为乳腺癌患者PRSS22表达量高低与总生存率关系图,B为多因素分析乳腺癌患者总生存率图,C为乳腺癌患者PRSS22表达量高低与无远处转移生存率关系图,D为多因素分析乳腺癌患者无远处转移生存率图。
具体实施方式
应该指出,以下详细说明都是示例性的,旨在对本发明提供进一步的说明。除非另有指明,本文使用的所有技术和科学术语具有与本发明所属技术领域的普通技术人员通常理解的相同含义。
需要注意的是,这里所使用的术语仅是为了描述具体实施方式,而非意图限制根据本发明的示例性实施方式。如在这里所使用的,除非上下文另外明确指出,否则单数形式也意图包括复数形式,此外,还应当理解的是,当在本说明书中使用术语“包含”和/或“包括”时,其指明存在特征、步骤、操作、器件、组件和/或它们的组合。
本发明的一个典型具体实施方式中,提供一种乳腺癌诊断和/或预后判断用mRNA标志物,所述mRNA标志物为PRSS22。
本发明的一个或多个具体实施方式中,所述标志物选自受试者乳腺组织或乳腺癌组织。
本发明通过研究发现PRSS22在乳腺癌中表达上调,PRSS22高表达的患者较低表达的患者预后不良,PRSS22是独立预后因子。
本发明的第二个典型具体实施方式中,提供用于检测上述标志物的物质在制备乳腺癌诊断和/或预后产品中的应用。
本发明的一个或多个具体实施方式中,检测上述标志物的物质可以是采用诸如ELISA、胶体金试纸条、蛋白芯片等现有检测待测样本中相关蛋白及多肽表达情况的物质。
本发明的一个或多个具体实施方式中,所述待测样本为人源样本;更具体的,所述待测样本为乳腺癌组织。
本发明的第三个典型具体实施方式中,提供一种用于乳腺癌诊断和/或预后判断的系统,所述系统包括∶
i)分析单元,所述分析单元包含∶用于确定受试者的待测样品中选自上述标志物表达水平的检测物质,以及;
ii)评估单元,所述评估单元包含∶根据i)中确定的所述标志物表达水平判断所述受试者患病情况;
所述待测样品包括受试者的乳腺癌病灶;
所述标志物为PRSS22。
本发明的一个或多个具体实施方式中,所述评估单元中,根据乳腺癌病灶中的PRSS22的表达情况,判断受试者是否患有乳腺癌诊断和/或判断受试者乳腺癌预后情况。
本发明的一个或多个具体实施方式中,所述受试者乳腺癌预后情况包括但不限于受试者生存率。
本发明的第四个典型具体实施方式中,提供一种诊断或辅助诊断乳腺癌的方法,所述方法包括∶
a)从受试者分离待测样品;
b)在所述受试者的待测样品中检测上述标志物的表达水平并判断所述受试者患病情况。
本发明的一个或多个具体实施方式中,所述待测样品包括受试者的乳腺组织或乳腺癌组织。
本发明的一个或多个具体实施方式中,所述标志物为PRSS22。
本发明的第五个典型具体实施方式中,提供一种乳腺癌患者预后情况判断方法所述判断方法包括检测患者病灶组织中PRSS22的含量。
为了使得本领域技术人员能够更加清楚地了解本发明的技术方案,以下将结合具体的实施例详细说明本发明的技术方案。
实施例1
一种乳腺癌诊断和/或预后判断用mRNA标志物的确定
GEPIA(http://gepia.cancer-pku.cn/index.html)是一个基因表达谱分析的网站,它整合了基于TCGA等数据库的RNA测序信息,可进行肿瘤与正常组织的基因差异表达分析。
UALCAN(http://ualcan.path.uab.edu/)是一个基于TCGA基因表达数据分析的网站,其整合了来源于TCGA的31种肿瘤的RNA测序及临床信息。
Kaplan Meier plotter(http://kmplot.com/analysis/index.php?p=background)是一可做生存分析的网络数据库,GOBO数据库(http://co.bmc.lu.se/gobo/gsa.pl)基于Affymetrix U133A芯片平台的乳腺肿瘤芯片数据,可进行单个及多个基因的表达水平与预后的关联分析。
(1)使用GEPIA、UALCAN分析PRSS22在乳腺癌等多种肿瘤及正常组织中的表达情况。
(2)基于Kaplan Meier plotter、GOBO数据分析PRSS22在乳腺癌中的预后价值。
如图1所示,GEPIA数据显示PRSS22在乳腺癌、宫颈癌、卵巢癌、子宫内膜癌、直肠癌、结肠癌、胆管癌、胃癌、胰腺癌、子宫内膜癌、肺癌、膀胱尿路上皮癌等数十种人类常见恶性肿瘤如中表达水平均高于其对应正常组织。
如图2所示,UALCAN数据显示PRSS22表达在乳腺癌组织(n=1097)中明显高于正常乳腺组织(n=114,P<0.001)。
如图3所示,Kaplan Meier plotter数据显示PRSS22高表达的乳腺癌患者的总生存时间(图3A,HR=1.29(1.03-1.61),P=0.024)、无远处转移生存时间(图3B,HR=1.35(1.09-1.66),P=0.0051)及复发后生存时间(图3C,HR=1.31(1.02-1.68),P=0.035)明显少于PRSS22低表达的患者。
如图4所示,GOBO数据显示PRSS22高表达的乳腺癌患者的总生存率(图4A,P=0.00158)及无远处转移生存率(图4C,P=0.00738)明显差于PRSS22低表达的患者。多因素分析(图4B)发现PRSS22、年龄、肿瘤直径、组织学分级及淋巴结转移是乳腺癌患者总生存的独立预后因子,其中PRSS22低表达提示预后较好(HR=0.66(0.5-0.89),P=0.006)。多因素分析(图4D)发现PRSS22、组织学分级及淋巴结转移是乳腺癌患者无远处转移生存的独立预后因子,其中PRSS22低表达提示预后较好(HR=0.66(0.49-0.88),P=0.005)。
以上所述仅为本发明的优选实施例而已,并不用于限制本发明,对于本领域的技术人员来说,本发明可以有各种更改和变化。凡在本发明的精神和原则之内,所作的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。
Claims (10)
1.一种乳腺癌诊断和/或预后判断用mRNA标志物,其特征在于,所述mRNA标志物为PRSS22。
2.如权利要求1所述标志物,其特征在于,所述标志物选自受试者乳腺癌组织。
3.检测权利要求1或2所述标志物的物质在制备乳腺癌诊断和/或预后产品中的应用。
4.如权利要求3所述的应用,其特征在于,待测样本为人源样本;优选的,所述待测样本为乳腺癌组织。
5.一种用于乳腺癌诊断和/或预后判断的系统,其特征在于,所述系统包括∶
i)分析单元,所述分析单元包含∶用于确定受试者的待测样品中选自上述标志物表达水平的检测物质,以及;
ii)评估单元,所述评估单元包含∶根据i)中确定的所述标志物表达水平判断所述受试者患病情况;
所述待测样品包括受试者的乳腺癌病灶;
所述标志物为PRSS22。
6.如权利要求5所述的系统,其特征在于,所述评估单元中,根据乳腺癌病灶中的PRSS22的表达情况,判断受试者是否患有乳腺癌诊断和/或判断受试者乳腺癌预后情况。
7.一种诊断或辅助诊断乳腺癌的方法,其特征在于,所述方法包括∶
a)从受试者分离待测样品;
b)在所述受试者的待测样品中检测上述标志物的表达水平并判断所述受试者患病情况。
8.如权利要求7所述的方法,其特征在于,所述待测样品包括受试者的乳腺腺体;
或,所述受试者乳腺癌预后情况包括但不限于受试者生存率。
9.如权利要求7所述的方法,其特征在于,所述标志物为PRSS22。
10.一种乳腺癌患者预后情况判断方法,其特征在于,所述判断方法包括检测患者病灶组织中PRSS22的含量。
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