中国医科大学学报

中国医科大学学报
  • 中文核心期刊
  • 中国科技核心期刊
  • 中国高校百佳科技期刊
  • BA、CA收录

中国医科大学学报 ›› 2018, Vol. 47 ›› Issue (4): 299-304.doi: 10.12007/j.issn.0258-4646.2018.04.003

• 论著 • 上一篇    下一篇

人激肽释放酶相关肽10 ELISA方法建立及其临床应用

杨帆1, 陈英剑2, 吴艳花2, 胡成进2   

  1. 1. 锦州医科大学研究生院, 辽宁 锦州 121001;
    2. 济南军区总医院实验诊断科, 济南 250031
  • 收稿日期:2017-06-16 出版日期:2018-04-30 发布日期:2018-04-10
  • 通讯作者: 胡成进 E-mail:hcj6289@163.com
  • 作者简介:杨帆(1990-),女,硕士研究生.
  • 基金资助:
    国家自然科学基金(81472497)

Establishment of a Method for Detecting Kallikrein 10 in the Serum and Its Clinical Application

YANG Fan1, CHEN Yingjian2, WU Yanhua2, HU Chengjin2   

  1. 1. Graduate School of Jinzhou Medical University, Jinzhou 121001, China;
    2. Department of Laboratory Medicine, General Hospital of Jinan Military Command Region, Jinan 250031, China
  • Received:2017-06-16 Online:2018-04-30 Published:2018-04-10

摘要: 目的 建立人激肽释放酶相关肽10(KLK10)双抗体夹心酶联免疫吸附试验(ELISA),并利用该方法初步探讨KLK10作为乳腺癌肿瘤标志物的临床价值。方法 建立KLK10双抗体夹心ELISA检测方法,对该方法进行方法学评估。采用本方法检测健康正常人群(健康对照组)、乳腺良性病女性患者、乳腺癌女性患者血清中KLK10含量,分析KLK10含量与乳腺癌临床病理特性的相关性及其临床应用价值。结果 利用KLK10 ELISA检测方法检测乳腺癌患者、乳腺良性病患者、健康对照组血清中KLK10含量分别为(0.88±0.45)、(1.35±0.56)、(1.57±0.88)ng/mL,3组比较具有统计学差异(均P < 0.05)。KLK10对乳腺癌具有较高的诊断灵敏度、准确率,其检测效能高于现有乳腺癌血清标志物。结论 成功建立了具有高灵敏度和特异性的KLK10双抗体夹心ELISA检测方法,可用于临床血清KLK10检测;KLK10与乳腺肿瘤的发生发展密切相关,有潜力成为乳腺肿瘤标志物。

关键词: 人激肽释放酶相关肽10, 乳腺癌, 血清标志物, ELISA, 诊断价值

Abstract: Objective To establish an ELISA method for detecting kallikrein 10 (KLK10) in the serum,and evaluate KLK10 as a biomarker for breast cancer. Methods The KLK10 ELISA assay was established and its efficiency was evaluated. Then,using this method, the serum KLK10 levels in all the samples were quantified. The correlation between KLK10 level and clinicopathological features,and the clinical value of KLK10 were analyzed. Results The serum KLK10 level in patients with breast cancer,patients with benign breast disease,and normal controls was found to be 0.88±0.45,1.35±0.56,and 1.57±0.88 ng/mL,respectively. The KLK10 levels in patients with breast cancer were significantly different from those in patients from the other groups (P < 0.05). The sensitivity,accuracy,and Youden index of KLK10 detection in the breast cancer samples were higher than those for CEA and CA 153 detection,which proved that KLK10 has potential as a new serum marker for breast cancer. Conclusion The KLK10 ELISA assay was established successfully and KLK10 could be detected in the serum samples. The presence of KLK10 in the serum was closely related to the occurrence and development of breast cancer,and KLK10 has potential as a marker for breast cancer.

Key words: kallikrein 10, breast cancer, serum marker, ELISA, diagnostic value

中图分类号: 

  • R446.6
[1] LUNDWALL A,BAND V,BLABER M,et al. A comprehensive nomenclature for serine proteases with homology to tissue kallikreins[J]. Biol Chem,2006,387(6):637-641. DOI:10.1515/BC.2006.082.
[2] SOTIROPOULOU G,PAMPALAKIS G,DIAMANDIS EP. Functional roles of human kallikrein-related peptidases[J]. Biol Chem,2009, 284(48):32989-32994. DOI:10.1074/jbc.R109.027946.
[3] CLEMENTS JA,WILLEMSEN NM,MYERS SA,et al. The tissue kallikrein family of serine proteases:functional roles in human disease and potential as clinical biomarkers[J]. Crit Rev Clin Lab Sci, 2004,41(3):265-312. DOI:10.1080/10408360490471931.
[4] DORN J,BEAUFORT N,SCHMITT M,et al. Function and clinical relevance of kallikrein-related peptidases and other serine proteases in gynecological cancers[J]. Crit Rev Clin Lab Sci,2014,51(2):63-84. DOI:10.3109/10408363.2013.865701.
[5] SCORILAS A,MAVRIDIS K. Predictions for the future of kallikrein-related peptidases in molecular diagnostics[J]. Expert Rev Mol Diagn, 2014,14(6):713-722. DOI:10.1586/14737159.2014.928207.
[6] PETRAKI CD,KARAVANA VN,LUO LY,et al. Human kallikrein 10 expression in normal tissues by immunohistochemistry[J]. J Histochem Cytochem,2002,50(9):1247-1261. DOI:10.1177/002215540205000912.
[7] LUO LY,GRASS L,HOWARTH DJ,et al. Immunofluorometric assay of human kallikrein 10 and its identification in biological fluids and tissues[J]. Clin Chem,2001,47(2):237-246.
[8] LI B,GOYAL J,DHAR S,et al. CpG methylation as a basis for breast tumor-specific loss of NES1/kallikrein 10 expression[J]. Cancer Res, 2001,61(21):8014-8021.
[9] GRIN A,SAMAAN S,TRIPATHI M,et al. Evaluation of human tissue kallikrein-related peptidases 6 and 10 expression in early gastroesophageal adenocarcinoma[J]. Hum Pathol,2015,46(4):541-548. DOI:10.1016/j.humpath.2014.12.005.
[10] JIAO X,LU HJ,ZHAI MM,et al. Overexpression of kallikrein gene 10 is a biomarker for predicting poor prognosis in gastric cancer[J]. World J Gastroenterol,2013,19(48):9425-9431. DOI:10.3748/wjg.v19.i48.9425.
[11] KOLIN DL,SY K,ROTONDO F,et al. Prognostic significance of human tissue kallikrein-related peptidases 6 and 10 in gastric cancer[J]. Biol Chem,2014,395(9):1087-1093. DOI:10.1515/hsz-2014-0143.
[12] LUO LY,BUNTING P,SCORILAS A,et al. Human kallikrein 10:a novel tumor marker for ovarian carcinoma?[J].Clin Chim Acta, 2001,306(1/2):111-118.
[13] ZHANG Y,BHAT I,ZENG M,et al. Human kallikrein 10,a predictive marker for breast cancer[J]. Biol Chem,2006,387(6):715-721. DOI:10.1515/BC.2006.090.
[14] 顾平,盛世乐,黄钢. 生物标志物在乳腺癌研究中的应用[J]. 上海交通大学(医学版),2007,127(11):1396-2004. DOI:10.3969/j.issn.1674-8115.2007.11.030.
[15] EWAN KING L,LI X,CHEIKH SAAD BOUH K,et al. Human kallikrein 10 ELISA development and validation in breast cancer sera[J]. Clin Biochem,2007,40(13/14):1057-1062. DOI:10.1016/j.clinbiochem.2007.05.008.
[16] YUNES MJ,NEUSCHATZ AC,BORNSTEIN LE,et al. Loss of expression of the putative tumor suppressor NES1 gene in biopsy-proven ductal carcinoma in situ predicts for invasive carcinoma at definitive surgery[J]. Int J Radiat Oncol Biol Phys,2003,56(3):653-657.
[17] GOLDHIRSCH A,WOOD WC,COATES AS,et al. Strategies for sub-types-dealing with the diversity of breast cancer:highlights of the St. Gallen international expert consensus on the primary therapy of early breast cancer 2011[J]. Ann Oncol,2011,22(8):1736-1747. DOI:10.1093/annonc/mdr304.
[18] KIOULAFA M,KAKLAMANIS L,STATHOPOULOS E,et al. Kallikrein 10(KLK10) methylation as a novel prognostic biomarker in early breast cancer[J]. Ann Oncol,2009,20(6):1020-1025. DOI:10.1093/annonc/mdr733.
[19] LUO LY,DIAMANDIS EP,LOOK MP,et al. Higher expression of human kallikrein 10 in breast cancer tissue predicts tamoxifen resist-ance[J]. Br J Cancer,2002,86(11):1790-1796. DOI:10.1038/sj.bjc.6600323.
[20] 阮贝鸿. 探索乳腺癌细胞系中曲妥珠单抗耐药相关的生物标志物[D].杭州:浙江大学,2016.
[21] 丁洁,何杨,杨剑锋,等. 双抗体夹心ELISA测定人血浆可溶性血管内皮钙黏蛋白方法的建立及其应用研究[J]. 中国实验血液学杂志,2017,25(2):562-566. DOI:10.7534/j.issn.1009-2137.
[22] BABLOK W,PASSING H,BENDER R,et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry,Part Ⅲ[J]. Clin Chem Clin Biochem,1988,26(11):783-790.
[23] TORRE LA,BRAY F,SIEGEL RL,et al. Global cancer statistics 2012[J]. CA Cancer J Clin,2015,65(2):87-108. DOI:10.3322/caac.21262.
[24] LIU XL,WAZER DE,WATANABE K,et al. Identification of a novel serine protease-like gene,the expression of which is down-regulated during breast cancer progression[J]. Cancer Res,1996,56(14):3371-3379.
[25] 赵晶,刘红,张爱敏,等. 乳腺癌患者血清可溶性肿瘤标志物的临床价值研究[J]. 中国肿瘤临床,2008,35(24):1411-1414. DOI:10.3969/j.issn.1000-8179.2008.24.010.
[26] 朱丽娜. 乳腺癌几种常用肿瘤标志物的研究意义[J]. 世界最新医学信息文摘,2015,15(71):43. DOI:10.3969/j.issn.1671-3141.2015.71.025.
[1] 程莉莉, 朱美琳, 董有静. 甲强龙联合雷莫司琼治疗全静脉麻醉下乳腺癌改良根治术患者术后恶心呕吐的效果[J]. 中国医科大学学报, 2019, 48(8): 756-759.
[2] 王硕, 郑新宇. 乳腺癌根治术患者化疗相关粒细胞减少与预后的关系[J]. 中国医科大学学报, 2019, 48(6): 542-546.
[3] 蔡恒, 刘文静, 冯天达, 刘云会. 垂体转移瘤的临床特点及治疗分析:2例病例报道及文献回顾[J]. 中国医科大学学报, 2019, 48(6): 564-567.
[4] 庄莹, 张淑红, 樊伟平, 赵小芳, 孙海燕, 刘爽, 张虎. 乳腺癌中DEAH盒解旋酶16的表达及临床意义[J]. 中国医科大学学报, 2019, 48(4): 305-308.
[5] 蔡存伟, 温媛媛, 李晓燕, 张丽娜. SIAH1核异位表达抑制乳腺癌细胞凋亡的作用机制[J]. 中国医科大学学报, 2019, 48(4): 328-332,337.
[6] 樊璐, 王慧, 肖庆桓. 跨膜蛋白16F对乳腺癌细胞增殖及迁移的影响[J]. 中国医科大学学报, 2019, 48(2): 124-127.
[7] 马金柱, 赵铁映, 刘明, 张瑞, 布日古德. 散发性乳腺癌与BRCA2基因rs206115位点多态性的相关分析[J]. 中国医科大学学报, 2019, 48(2): 149-152,158.
[8] 刘叶, 刘诗盈, 冯冬东, 李丽莉, 徐蕾, 王爱平. 内分泌治疗期间创新途径随访对提高乳腺癌患者自我效能和韧性水平的影响[J]. 中国医科大学学报, 2019, 48(1): 85-86.
[9] 杨帆, 陈英剑, 亓敏, 胡成进. 应用液体蛋白芯片-飞行时间质谱技术诊断乳腺癌的临床价值[J]. 中国医科大学学报, 2018, 47(6): 490-493,512.
[10] 张苏宁, 刘宗昂. 小细胞肺癌中DBC1的表达及预后相关性研究[J]. 中国医科大学学报, 2018, 47(3): 222-225.
[11] 贡鸣, 何天宇, 裘敬平, 李光. 6种常见肿瘤患者初治时外周血T淋巴细胞亚群数量及临床特征[J]. 中国医科大学学报, 2018, 47(12): 1119-1122.
[12] 刘力, 孙清雨. 草酸艾司西酞普兰治疗乳腺癌伴抑郁症患者的效果[J]. 中国医科大学学报, 2018, 47(11): 1021-1024.
[13] 吴子敬, 刘叶, 李小寒. 乳腺癌患者心理韧性现状及其与焦虑抑郁之间的关系[J]. 中国医科大学学报, 2018, 47(1): 78-81.
[14] 邹丹 ,冯秀艳 ,周伟强. 乳腺癌 MCF-7 细胞 p21WAF1/CIP1 启动子区雌激素受体 α 的高功能结合位点[J]. 中国医科大学学报, 2017, 46(8): 677-680.
[15] 刘诗盈 ,王爱平 ,金锋 ,徐蕾 ,穆晓云 ,景丽伟. 乳腺癌患者内分泌治疗依从性和服药信念的现状及相关性研究[J]. 中国医科大学学报, 2017, 46(8): 698-702.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 郭哲, 徐冰, 卢利. 下颌骨髁突骨折治疗的Meta分析[J]. 中国医科大学学报, 2009, 38(9): 709 .
[2] 夏永辉, 徐克. 对吻式支架置入术治疗Leriche综合征15例体会[J]. 中国医科大学学报, 2009, 38(9): 714 .
[3] 林书坡, 林杰, 史今. 替米沙坦对胰岛素抵抗大鼠肾脏脂联素表达的影响[J]. 中国医科大学学报, 2009, 38(10): 741 .
[4] 高红, 吕良英, 白伟良, 王大佳, 黄英, 张志波, 王维林. 先天性巨结肠组织蛋白质组成分的双向凝胶电泳分析[J]. 中国医科大学学报, 2009, 38(10): 761 .
[5] 刘鹏辉, 廖国清, 李月敏, 尹艳慧, 王红梅, 曲怡梅. 肺癌患者外周血BJ-TSA-9,LUNX和CK19 mRNA的检测及其临床意义[J]. 中国医科大学学报, 2009, 38(10): 786 .
[6] 张华, 王秋月, 侯刚, 许惟元, 李猛, 康健. 辽宁部分农村地区居民吸烟情况与COPD患病关系的调查[J]. 中国医科大学学报, 2009, 38(11): 855 .
[7] 李黎黎, 王哲. 发育和健康状况评定量表在儿童青少年抑郁障碍中的应用[J]. 中国医科大学学报, 2009, 38(11): 865 .
[8] 孙毅, 蒋丽娟, 肖华凤, 任奕. 老年重症社区获得性肺炎临床特点及预后因素[J]. 中国医科大学学报, 2009, 38(12): 946 .
[9] 张依宁, 魏敏杰, 孙明军. 伊立替康抑制人结直肠癌细胞增殖和ATP敏感性钾通道的相关性研究[J]. 中国医科大学学报, 2010, 39(1): 10 .
[10] 黄海能, 罗起胜, 赵邦, 谭源福, 邓元央, 黄华东, 符黄德, 李传玉. 兔脑创伤后早期血清β淀粉样前体蛋白动态变化的实验研究[J]. 中国医科大学学报, 2010, 39(1): 22 .

中国医科大学学报版权所有©2018

未经允许,严禁擅自转载本站图文资料

地址:中国 沈阳市沈北新区蒲河路77号 110122

辽ICP备05014850

JOURNAL OF CHINA MEDICAL UNIVERSITY

ADDRESS: NO.77 PUHE ROAD

SHENYANG NORTH NEW AREA, SHENYANG

LIAONING PROVINCE, P.R. CHINA