CN113933510A - G蛋白偶联受体lpar6在肺癌预后中的用途 - Google Patents
G蛋白偶联受体lpar6在肺癌预后中的用途 Download PDFInfo
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- CN113933510A CN113933510A CN202110907152.XA CN202110907152A CN113933510A CN 113933510 A CN113933510 A CN 113933510A CN 202110907152 A CN202110907152 A CN 202110907152A CN 113933510 A CN113933510 A CN 113933510A
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Abstract
本发明公开了G蛋白偶联受体LPAR6在肺癌预后中的用途,本发明中LPAR6的表达与肺癌患者的预后明显正相关,即在肺癌患者的癌组织中LPAR6的表达越高,患者的预后越好,通过多因素COX生存分析构建了影响肺癌患者预后的模型,K‑M plot曲线、ROC曲线及患者的生存时间都验证了模型的准确性和特异性。因此该标志物在肺癌中作为预后指标具有一定的潜在应用价值,可进一步为肺癌患者的个性化治疗选择提供依据,对采取个性化的治疗和降低肺癌死亡率具有重要的意义。
Description
技术领域
本发明属于生物医药领域,涉及G蛋白偶联受体LPAR6在肺癌预后中的用途,更具体地,涉及G蛋白偶联受体LPAR6作为肺癌预后标志物及其应用。
背景技术
肺癌是全世界最常见的恶性肿瘤之一,其致死率在所有恶性肿瘤中位居第一,转移是导致不良预后的关键生物学过程。该疾病严重威胁国人的生命和健康,且发病年龄构成年轻化,每年用于肺腺癌治疗的医疗支出大为增加,肺腺癌成了严重危害我国人民生命财产安全的头号敌人,并且是影响社会经济发展的一个重要因素(Siegel RL,Miller KD,Fuchs HF,Jemal A.Cancer statistics,2021.CA Cancer J Clin.2021;71(1):7-33.)。尽管全球肺腺癌患者的五年生存率逐渐上升,但我国目肺癌患者的5年生存率依然不足10%,不容乐观。
根据组织病理学分类,肺癌可分为两大亚型:小细胞肺癌和非小细胞肺癌,其中非小细胞肺癌更为普遍。肺鳞状细胞癌和肺腺癌是两种最常见的非小细胞肺癌亚型(American Cancer Society.Key statistics for lung cancer.www.cancer.org/cancer/non-small-cell-lung-cancer/about/key-statistics.html)。手术是非小细胞肺癌早期的主要治疗选择,而在晚期主要选择手术结合化疗或/和放疗。然而,尽管采用了这些治疗方法,患者的预后仍然不佳,而且治疗后复发是该疾病的主要特征及主要的致死原因(Dela Cruz CS,Tanoue LT,Matthay RA.Lung cancer:epidemiology,etiology,andprevention.Clin Chest Med.2011;32(4):605-44.)。所以及早发现、及早治疗以及精准的术后检测追踪对于提高患者生存率至关重要。
到目前为止,已有数十种的基因异常表达或者蛋白水平异常被确定与肺癌的发生发展有关,但是缺乏足够的生物标志物对肺癌患者,特别是对于传统的治疗方法如外科切除术等受到了限制的肺癌晚期患者的预后进行检测。鉴于此,开发一种新型生物标志物对于肺癌的预后监测乃至靶向治疗至关重要。
溶血磷脂酸(LPA)是一种参与肿瘤增殖的脂质,2019年前共发现其有五种受体,分别为LPAR1-5,LPAR6是LPA家族的最新发现的受体,作为一种G蛋白偶联受体(GPCR)(Taniguchi R,Inoue A,Sayama M,Uwamizu A,Yamashita K,Hirata K,Yoshida M,etal.Structural insights into ligand recognition by the lysophosphatidic acidreceptor LPA6.Nature.2017;548(7667):356-60.Shimomura Y,Wajid M,Ishii Y,Shapiro L,Petukhova L,Gordon D,et al.Disruption of P2RY5,an orphan G protein-coupled receptor,underlies autosomal recessive woolly hair.Nat Genet.2008;40(3):335-9.),LPAR6已被揭示与多种类型的癌症相关,包括结直肠癌、前列腺癌、胰腺癌(Takahashi K,Fukushima K,Onishi Y,Inui K,Node Y,Fukushima N,etal.Lysophosphatidic acid(LPA)signaling via LPA4 and LPA6negatively regulatescell motile activities of colon cancer cells.Biochem Biophys Res Comm.2017;483(1):652-7.Sokolov E,Eheim AL,Ahrens WA,et al.Lysophosphatidic acidreceptor expression and function in human hepatocellular carcinoma.J SurgRes.2013;180(1):104-13.)。然而,LPAR6的功能仍然存在很大争议。LPAR6在结直肠癌中充当肿瘤抑制因子并抑制肿瘤迁移,而在提到的其他肿瘤中,LPAR6蛋白可能充当促进剂(Ketscher A,Jilg CA,Willmann D,et al.LSD1 controls metastasis of androgen-independent prostate cancer cells through PXN and LPAR6.Oncogenesis.2014;3:e120.Ishii S,Hirane M,Fukushima K,et al.Diverse effects of LPA4,LPA5 and LPA6on the activation of tumor progression in pancreatic cancer cells.BiochemBiophys Res Comm.2015;461(1):59-64.)。所有这些发现表明LPAR6编码的蛋白质可能在癌症中发挥重要作用,但LPAR6与肺癌进展之间的关联及其潜在机制未有相关报道。因此,为诊断和预后监测目的研究和开发在肺癌中异常表达的基因和/或蛋白具有重要意义。
发明内容
为了实现上述目的,本发明提供了一种G蛋白偶联受体LPAR6在肺癌预后中的用途。
本发明的技术方案为:
鉴定试剂在制备预测肺腺癌预后的产品中的用途,其中:所述的鉴定试剂特异性地确定G蛋白偶联受体LPAR6基因或其表达产物在受试者样本中的存在和/或水平。
进一步地,所述的肺癌为非小细胞肺癌。更进一步地,所述的肺癌为肺腺癌或肺鳞癌。
在一些实施方式中,所述的受试者是哺乳动物,例如但不限于:人、小鼠、大鼠、豚鼠、兔、牛、羊、马、骆驼、猪、犬、猫、猴或猿。在一些具体的实施方式中,所述的哺乳动物是人。
在一些实施方式中,所述G蛋白偶联受体LPAR6是人的G蛋白偶联受体LPAR6。人G蛋白偶联受体LPAR6的核苷酸序列可以在公共数据库中获得,Gene ID为10161。
在一些实施方式中,G蛋白偶联受体LPAR6基因的表达产物是指,G蛋白偶联受体LPAR6基因在其生命周期中任意阶段的任意形式,例如但不限于:G蛋白偶联受体LPAR6的mRNA或其互补序列、G蛋白偶联受体LPAR6的cDNA(如SEQ ID NO:1所示)或其互补序列、G蛋白偶联受体LPAR6的成熟蛋白(如SEQ ID NO:2所示)、G蛋白偶联受体LPAR6的前体蛋白、或上述任一形式的片段、突变体、衍生物或修饰产物。
在一些实施方式中,所述的水平是蛋白质水平,尤其是针对肺腺癌或肺鳞癌;在这些实施方案中,鉴定试剂可基于本领域已知的定量或定性免疫测定方案鉴定蛋白质水平,免疫测定形式可以包括,但不限于,酶联免疫吸附测定(ELISA)、放射性免疫测定(RIA)、夹心测定、蛋白质印迹、免疫沉淀、免疫组织化学染色、流式细胞术、荧光辅助的细胞分选(FACS)、酶底物显色测定和抗原-抗体聚集。
作为实例,鉴定试剂包括特异性结合G蛋白偶联受体LPAR6基因编码蛋白的抗体或其片段。可以使用任何结构、尺寸、免疫球蛋白类别、起源等的抗体或其片段,只要它结合靶蛋白质即可。本发明的产品中包括的抗体或其片段可以是单克隆的或多克隆的。抗体片段指保留抗体对抗原的结合活性的抗体一部分(部分片段)或含有抗体一部分的肽。抗体片段可以包括F(ab′)2、Fab′、Fab、单链Fv(scFv)、二硫化物键合的Fv(dsFv)或其聚合物、二聚化V区(双抗体)、或含有CDR的肽。本发明的鉴定试剂可以包括编码抗体或编码抗体片段的氨基酸序列的分离的核酸,包含该核酸的载体,和携带该载体的细胞。
在另一些实施方式中,所述的水平是核酸水平,尤其是针对肺腺癌;在这些实施方案中,鉴定试剂可基于使用核酸分子的已知方法来发挥其功能:如PCR、如Southern杂交、Northern杂交、点杂交、荧光原位杂交(FISH)、DNA微阵列、ASO法、高通量测序平台等。使用本发明的产品可以定性地、定量地、或半定量地实施分析。
在一些实施方式中,所述的样本选自为肿瘤组织,例如,通过组织活检、冷冻保存样本、冰冻切片样本、福尔马林保存组织等方式获得或保存的肿瘤组织。
在一些实施方式中,本发明的产品可以是试剂、试剂盒、芯片、试纸、孔板、胶乳颗粒、磁珠等。
在一些实施方案中,预后是指选自以下的一种或组合:预后受试者的结局、预后受试者的治疗效果、预后受试者的生存。
在一些具体的实施方案中,“预后”是指癌症患者在通过手术处理等抑制或缓解肿瘤生长后的过程或结果。在本说明书中,预后可以是通过手术处理抑制或缓解肿瘤生长后1、2、3、4、5、6、7、8、9、10、15、20年或更久时的生机状态。预后可以通过检测G蛋白偶联受体LPAR6来预测。
预后预测可以这样进行:基于G蛋白偶联受体LPAR6基因或其表达产物的在肺腺癌患者样本中的水平与肺腺癌患者预后正相关,在肺鳞癌患者样本中的水平并未表现出与肺鳞癌患者的预后具有相关性。确定肺腺癌患者的预后是良好还是不良,或者确定良好预后或不良预后的概率。例如,在此实施方式中,可以使用四分位数分析,在进行基因分组的时候,使用表达的前25%作为高表达组,后25%作为低表达组。
在本发明中,“预后良好”是指在通过手术处理等为患者抑制或缓解肿瘤生长之后,患者长时期(例如3、5、6、7、8、9、10、15、20年或更长)没有危急状况。或者,预后好可以意指在这样长时间内存活、无转移、无复发、或无再发。例如,预后良好可以意指至少3年或尤其是至少5年存活,优选没有转移或复发。预后良好最优选的状态是长期无疾病的存活。如本文中所使用的,“预后良好”还可以包括任何这样的状态,其中可以发现疾病如转移,但是恶性低且不严重地影响生存能力。
在本发明中,“预后不良”是指患者在通过手术处理等抑制或缓解肿瘤生长后的短时期(例如1、2、3、4、5年或更短)内发生致命状况。或者,预后差是指在这样的短时期里死亡、转移、复发、或再发。例如,预后差可以意指至少3年或尤其至少5年内复发、转移、或死亡。
预测预后是指预测患者状况的过程或结果,并不意味着能以100%的准确度预测患者状况的过程或结果。预测预后是指确定某些过程或结果的可能性是否增加,而并不意味着通过与某些过程或结果不发生的情况比较来确定发生某些过程或结果的可能性。
由于现有技术缺乏足够的生物标志物以便对肺腺癌患者的预后做出预测,尤其是对于肺腺癌晚期的患者,传统的治疗方法如肝移植、外科肝切除术、早期射频治疗等受到了限制。因此,开发一种新型生物标志物对于肺腺癌的预后监测乃至靶向治疗至关重要。本发明提供了一种作为G蛋白偶联受体的mRNA作为肺腺癌预后标志物并建立了预测肺腺癌患者预后的模型。最后,通过K-Mplot曲线,ROC曲线及患者的生存时间和生存状态验证了模型的准确性和特异性。
附图说明
图1是根据本发明实施例的LPAR6基因在肺腺癌和肺鳞癌患者的癌和癌旁组织中的表达量情况。
图2是本发明实施例中肺腺癌和肺鳞癌患者癌组织及正常组织中LPAR6的蛋白水平。
图3A是根据本发明实施例的肺腺癌患者的LPAR6基因表达情况将肺癌患者绘制的K-M plot总生存期曲线。
图3B是根据本发明实施例的肺鳞癌患者的LPAR6基因表达情况将肺癌患者绘制的K-M plot无进展生存期曲线。
图3C根据本发明实施例的肺腺癌患者的LPAR6基因表达情况将肺腺癌患者绘制的K-M plot总生存期曲线。
图3D根据本发明实施例的肺鳞癌患者的LPAR6基因表达情况将肺鳞癌患者绘制的K-M plot无进展生存期曲线。
图4A是根据本发明实施例的肺腺癌患者的LPAR6蛋白水平情况将肺腺癌患者绘制的K-M plot生存曲线。
图4B是根据本发明实施例的肺鳞癌患者的LPAR6蛋白水平情况将肺鳞癌患者绘制的K-M plot生存曲线。
具体实施方式
以下结合附图,通过实施例进一步说明本发明,但不作为对本发明的限制。以下提供了本发明实施方案中所使用的具体材料及其来源。但是,应当理解的是,这些仅仅是示例性的,并不意图限制本发明,与如下试剂和仪器的类型、型号、品质、性质或功能相同或相似的材料均可以用于实施本发明。下述实施例中所使用的实验方法如无特殊说明,均为常规方法。下述实施例中所用的材料、试剂等,如无特殊说明,均可从商业途径得到。
一、材料和方法
1.LPAR6基因表达水平测定
本发明实施例通过TIMER平台(Li T,Fan J,Wang B,Traugh N,Chen Q,Liu JS,etal.TIMER:a web server for comprehensive analysis of tumor-infiltrating immunecells.Cancer Res.2017;77:e108-10.)对LPAR6在各种癌症中的基因表达量进行分析,并且比较在癌和正常组织中的表达量差异。阈值设置如下:p值为1E-6,倍数变化为2,基因排名前5%。
2.肺腺癌和肺鳞癌患者预后分析
通过PrognoScan和GEPIA2(Hideaki Mizuno,Kunio Kitada,Kenta Nakai andAkinori Sarai.PrognoScan:a new database for meta-analysis of the prognosticvalue of genes.BMC Medical Genomics.2009;2:18.Tang,Z,Kang B,Li C,Chen T,ZhangZ.GEPIA2:an enhanced web server for large-scale expression profiling andinteractive analysis.Nucleic Acids Res.2019;47(W1):W556-60.)确定了肺腺癌和肺鳞癌中LPAR6基因表达与生存之间的关系。将阈值调整为<0.05的Cox p值。
3.蛋白水平与预后相关性分析
共计202名肺腺癌和肺鳞癌患者入组,根据实验数据以及病理信息和预后信息的完整新,确立80例肺腺癌和80例肺鳞癌患者作为证实试验分析样本。在手术后的60个月随访周期内。80例肺腺癌患者中有30个生存,50个死亡;80例肺鳞癌患者中有29生存,51个死亡。我们收集了患者手术切除的癌组织和相邻的癌旁组织,石蜡包埋,并制作成组织芯片,并对组织芯片进行免疫组化染色,并对结果进行打分判读并分析LPAR6蛋白水平与肺腺癌和肺鳞癌患者的预后关系。肺腺癌及肺鳞癌患者的临床资料分别见表1和表2。
表1肺腺癌患者信息
表2肺鳞癌患者信息
4.统计分析
通过TIMER产生的结果显示为p值和倍数变化。PrognoScan、Kaplan-Meier图和GEPIA的结果显示为HR和p/Cox p值。分析基因表达的相关系数,p值<0.05被认为具有统计学意义。Kaplan-Meier图和相应的对数秩检验用于评估组间OS的差异。肺腺癌和肺鳞癌患者的组织芯片判读方法如下:先从整体检测染色的情况,以明确染色部位及着色的程度和部位。本实施例中,LPAR6染色集中于薄膜,符合G蛋白偶联受体的特征。通过与间质作为对比来评判染色程度,可分为1-3三个级别,1为轻度染色,2为中度染色,3为重度染色。可以根据染色的整体情况,做出判断。再看染色的阳性细胞的比例,0-25%可以认为是1,26-50%可以认为是2,51-75%可以认为是3,75%以上可以认为是4。染色得分:染色程度乘于阳性细胞的比例。0-3为低表达,4-5为中表达,6以上可以认为是高表达。并按如下方法进行统计分析:将染色得分以中低表达,高表达等分组与病人的生存期相联系,做出一个生存曲线,可以得到一个结果。将染色得分以中低表达,高表达等分组,两组对比可以得出一个结果。将染色得分以中低表达,高表达等分组,与病人的TNM分期做出一个表格,可以得出一个结果。将染色得分以中低表达,高表达等分组,与病人的分化做出一个表格,可以得出一个结果。将染色得分以中低表达,高表达等分组,与病人的其他指标联系做出一个表格,可以得出一个结果。
二、实验结果
1.LPAR6在肺腺癌患者的癌组织和正常组织之间表达量存在差异
为了评估LPAR6在肺腺癌患者中的表达情况,本发明实施例使用TCGA中肺腺癌的RNA测序数据分析了LPAR6的基因表达量。研究纳入的两种亚型的肺癌患者(腺癌和鳞癌)的癌组织和邻近正常组织之间的LPAR6基因差异表达,如图1所示。LPAR6在肺腺癌患者的癌组织的基因表达量显著低于正常组织的表达量,在肺鳞癌患者中未见显著差异(图1)。
2.LPAR6是一种细胞膜表达的蛋白,在肺癌患者的癌组织和正常组织之间蛋白水平存在差异。本发明实施例中,可以看到染色集中于细胞膜上,LPAR6在癌组织普遍水平较低甚至检测不到,低于正常组织(图2)。
3.LPAR6基因表达量与肺腺癌患者预后正相关
本发明实施例分析了LPAR6基因表达是与肺癌预后的关系,基于Affymetrix微阵列和RNA测序数据,采用Kaplan-Meier Plotter数据库来确定LPAR6与肺癌预后的关系。本发明实施例中LPAR6基因表达量与肺癌患者的总生存期和无进展生存期都正相关,即LPAR6基因表达量高,肺癌患者预后好(图3A,图3B)。在肺癌的亚型中,LPAR6基因表达量与肺腺癌患者的总生存期正相关,即LPAR6基因表达量高,肺癌患者预后好(图3C),但是在肺鳞癌患者中未表现出具有显著差异的正相关性(图3D)。
4.LPAR6的蛋白水平与肺癌患者预后正相关
本实施例通过分析肺腺癌及肺鳞癌患者的LPAR6蛋白水平与预后之间的关系,得出LPAR6蛋白水平与基因表达水平在与肺腺癌和肺鳞癌患者的预后上都具有正相关性,即LPAR6蛋白水平高,两种肺癌患者具有良好预后(图4A和图4B)。结合实验结果3,本实施例中LPAR6的基因表达水平和蛋白水平对肺腺癌患者的预后均具有指导意义(图3C和图4A),LPAR6的蛋白水平对肺鳞癌患者的预后具有指导意义(图4B)。
综上所述,本发明有效克服了现有技术中的种种缺点而具高度产业利用价值。
除非另外说明,本发明中所公开的实验方法、检测方法、制备方法均采用本技术领域常规的分子生物学、生物化学、染色质结构和分析、分析化学、细胞培养、重组DNA技术及相关领域的常规技术。
以上示例性实施方式所呈现的描述仅用以说明本发明的技术方案,并不想要成为毫无遗漏的,也不想要把本发明限制为所描述的精确形式。显然,本领域的普通技术人员根据上述教导做出很多改变和变化都是可能的。选择示例性实施方式并进行描述是为了解释本发明的特定原理及其实际应用,从而使得本领域的其它技术人员便于理解、实现并利用本发明的各种示例性实施方式及其各种选择形式和修改形式。本发明的保护范围意在由所附权利要求书及其等效形式所限定。
序列表
<110> 上海交通大学
<120> G蛋白偶联受体LPAR6在肺癌预后中的用途
<130> 2021
<160> 2
<170> SIPOSequenceListing 1.0
<210> 1
<211> 2876
<212> DNA
<213> Homo sapiens
<400> 1
gaggtttctg gagggtgtgg cccccagagg gcatggaagc tctgcacccc tgctcccata 60
cctcacccta cgcatctcct catctgtatc ctttgcaata tcctttgtaa taaaccgaaa 120
attttatcat aatgagcatc aaaagaatcc caaatgagaa aactgctttt tgcataagtg 180
taaattaaga gatggaagtc acatttcacc atggcaaaca tttgctgcat gcaaaatgac 240
tgaaacaagg tcttgatctg tcaccaggct gaagtgcagt ggtacaatca aagctcactg 300
cagtctcaac ctcctaggct caaacaatcc tcccacttca gcctcccaac cagctgggac 360
cacaggttga catcaccaca cccaggtctg ctggaatttg ctggaggtcc actccagacc 420
ctgtttgtct ggatatcacc agcagaggtt gcagaacaac aaagattgct gcctgttcct 480
tcctctggaa gctttgtccc agaggggcac ccaccagacg gcagctggag ctctcctgtg 540
tgccactgga gtacgaaaaa gaaaaaatcc tgcagctagc tcggtgtctg cccaaacggc 600
tgcccagttt tgtgcttgaa acccagggcc tgggtggtgt aggcacccga gggaattgcc 660
tggtctaagg gttgtgaaga tcacggaaaa ggcatagagt ctgggccgga atgcatcgtt 720
cctcgtggca cattccctca tggcttccct tagctagggg aggaagttcc ctggcccctt 780
gcacttcccg ttccctctgc tatggctctt cctcagtaga aacaactggc aacaaaattc 840
aagtttatga ttcattcatc agcaaacatg tgagaatcat ctacaaagaa ccaagaattg 900
tgagaaagcg acctcaagat acaactggca actgaggaaa aggcctcaat tcaacaagag 960
ctaacaagct tgggagttta tttcggaatc tttaaaagac tcttctgctt acccacaatc 1020
tgggatccac tgcaggaaaa caaaaaagga aaacttcatt taaaagaagc aagaagtaaa 1080
atgggacaaa ttgggaatgt ttaagtctct gaaactctgc actgaaaaga aaataagatt 1140
gataacttaa gcttaacatt ctgaggcata aagaaacatt aactttggag tattcatctt 1200
gactactgaa atacaagttt agaagacaag tggtttcatt ctggtcacag atcacagctt 1260
ttctttaaat ttataatcct atgggttgga ctcgttgact gtatttttta aaggttgctc 1320
gtcagttaac tgagccttgg aattcatgga ttttctaaag actaacaaat gaaaatattt 1380
tcctgttgaa gaacccagcg gaaattttac agcaacaaat ttcatgtttc ttttgggtat 1440
ttctgagaaa aaggaaatat ttataaaacc atccaaagat ccagataatt tgcaaataaa 1500
ttggaggtta tagaggttat aatctgaatc ccaaaggaga ctgcagctga tgaaagtgct 1560
tccaaactga aaattggacg tgcctttacg atggtaagcg ttaacagctc ccactgcttc 1620
tataatgact cctttaagta cactttgtat gggtgcatgt tcagcatggt gtttgtgctt 1680
gggttaatat ccaattgtgt tgccatatac attttcatct gcgtcctcaa agtccgaaat 1740
gaaactacaa cttacatgat taacttggca atgtcagact tgctttttgt ttttacttta 1800
cccttcagga ttttttactt cacaacacgg aattggccat ttggagattt actttgtaag 1860
atttctgtga tgctgtttta taccaacatg tacggaagca ttctgttctt aacctgtatt 1920
agtgtagatc gatttctggc aattgtctac ccatttaagt caaagactct aagaaccaaa 1980
agaaatgcaa agattgtttg cactggcgtg tggttaactg tgatcggagg aagtgcaccc 2040
gccgtttttg ttcagtctac ccactctcag ggtaacaatg cctcagaagc ctgctttgaa 2100
aattttccag aagccacatg gaaaacatat ctctcaagga ttgtaatttt catcgaaata 2160
gtgggatttt ttattcctct aattttaaat gtaacttgtt ctagtatggt gctaaaaact 2220
ttaaccaaac ctgttacatt aagtagaagc aaaataaaca aaactaaggt tttaaaaatg 2280
atttttgtac atttgatcat attctgtttc tgttttgttc cttacaatat caatcttatt 2340
ttatattctc ttgtgagaac acaaacattt gttaattgct cagtagtggc agcagtaagg 2400
acaatgtacc caatcactct ctgtattgct gtttccaact gttgttttga ccctatagtt 2460
tactacttta catcggacac aattcagaat tcaataaaaa tgaaaaactg gtctgtcagg 2520
agaagtgact tcagattctc tgaagttcat ggtgcagaga attttattca gcataaccta 2580
cagaccttaa aaagtaagat atttgacaat gaatctgctg cctgaaataa aaccattagg 2640
actcactggg acagaacttt caagttcctt caactgtgaa aagtgtcttt ttggacaaac 2700
tatttttcca cctccaaaag aaattaacac atggacattt taaagtcttt agtataaaga 2760
aaatttgtat tcaatgtgtt aagcattaac atgtatttta tttgtgtatc cactccatct 2820
gatttttctg agccattttg atttgttcct tcattaaaaa aaatctctta aagtta 2876
<210> 2
<211> 344
<212> PRT
<213> Homo sapiens
<400> 2
Met Val Ser Val Asn Ser Ser His Cys Phe Tyr Asn Asp Ser Phe Lys
1 5 10 15
Tyr Thr Leu Tyr Gly Cys Met Phe Ser Met Val Phe Val Leu Gly Leu
20 25 30
Ile Ser Asn Cys Val Ala Ile Tyr Ile Phe Ile Cys Val Leu Lys Val
35 40 45
Arg Asn Glu Thr Thr Thr Tyr Met Ile Asn Leu Ala Met Ser Asp Leu
50 55 60
Leu Phe Val Phe Thr Leu Pro Phe Arg Ile Phe Tyr Phe Thr Thr Arg
65 70 75 80
Asn Trp Pro Phe Gly Asp Leu Leu Cys Lys Ile Ser Val Met Leu Phe
85 90 95
Tyr Thr Asn Met Tyr Gly Ser Ile Leu Phe Leu Thr Cys Ile Ser Val
100 105 110
Asp Arg Phe Leu Ala Ile Val Tyr Pro Phe Lys Ser Lys Thr Leu Arg
115 120 125
Thr Lys Arg Asn Ala Lys Ile Val Cys Thr Gly Val Trp Leu Thr Val
130 135 140
Ile Gly Gly Ser Ala Pro Ala Val Phe Val Gln Ser Thr His Ser Gln
145 150 155 160
Gly Asn Asn Ala Ser Glu Ala Cys Phe Glu Asn Phe Pro Glu Ala Thr
165 170 175
Trp Lys Thr Tyr Leu Ser Arg Ile Val Ile Phe Ile Glu Ile Val Gly
180 185 190
Phe Phe Ile Pro Leu Ile Leu Asn Val Thr Cys Ser Ser Met Val Leu
195 200 205
Lys Thr Leu Thr Lys Pro Val Thr Leu Ser Arg Ser Lys Ile Asn Lys
210 215 220
Thr Lys Val Leu Lys Met Ile Phe Val His Leu Ile Ile Phe Cys Phe
225 230 235 240
Cys Phe Val Pro Tyr Asn Ile Asn Leu Ile Leu Tyr Ser Leu Val Arg
245 250 255
Thr Gln Thr Phe Val Asn Cys Ser Val Val Ala Ala Val Arg Thr Met
260 265 270
Tyr Pro Ile Thr Leu Cys Ile Ala Val Ser Asn Cys Cys Phe Asp Pro
275 280 285
Ile Val Tyr Tyr Phe Thr Ser Asp Thr Ile Gln Asn Ser Ile Lys Met
290 295 300
Lys Asn Trp Ser Val Arg Arg Ser Asp Phe Arg Phe Ser Glu Val His
305 310 315 320
Gly Ala Glu Asn Phe Ile Gln His Asn Leu Gln Thr Leu Lys Ser Lys
325 330 335
Ile Phe Asp Asn Glu Ser Ala Ala
340
Claims (9)
1.鉴定试剂在制备预测肺癌预后的产品中的用途,其中,所述的鉴定试剂特异性地确定G蛋白偶联受体LPAR6基因或其表达产物在受试者样本中的存在和/或水平。
2.根据权利要求1所述的用途,其中,所述的肺癌为非小细胞肺癌。
3.根据权利要求2所述的用途,其中,所述的非小细胞肺癌为肺腺癌;所述的水平是核酸水平或者蛋白质水平。
4.根据权利要求2所述的用途,其中,所述的非小细胞肺癌为肺鳞癌;所述的水平是蛋白质水平。
5.根据权利要求1至4中任一项所述的用途,其中,所述的G蛋白偶联受体LPAR6是人的G蛋白偶联受体LPAR6,其Gene ID为10161。
6.根据权利要求5所述的用途,其中,所述的样本为肿瘤组织。
7.根据权利要求5所述的用途,其中,所述的产品为试剂、试剂盒、芯片、试纸、孔板、胶乳颗粒或磁珠。
8.根据权利要求5所述的用途,其中,所述的预后是指选自以下的一种或组合:预后受试者的结局、预后受试者的治疗效果、预后受试者的生存。
9.根据权利要求6至8中任一项所述的用途,其中,G蛋白偶联受体LPAR6基因或其表达产物的在受试者样本中的水平,与受试者肺癌预后正相关。
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