登录    
  
首页 > 期刊论文 > 论文摘要
结直肠癌化疗敏感性相关蛋白的蛋白质组学初步研究
         
Proteomic identification of chemosensitivity-associated proteins in human colorectal carcinomas

摘    要
目的: 本研究应用蛋白质组学技术建立化疗敏感性不同的结直肠癌组织总蛋白双向凝胶电泳(two-dimensional gel electrophoresis, 2-DE)图谱, 并鉴定部分差异表达蛋白, 以发现与结直肠癌化疗敏感性有关的蛋白。方法: 收集临床诊断为晚期结直肠癌的病例, 肠镜活检获取新鲜结直肠癌标本后液氮保存备用, 根据肿瘤药物敏感实验分为化疗高敏感组和化疗低敏感组。提取组织总蛋白, 采用双向凝胶电泳技术得到各组凝胶图谱;采用PD-quest 7.3软件进行图像的合成、对比和差异分析, 识别化疗高敏感组和化疗低敏感组之间差异表达的蛋白斑点;选取差异蛋白质点, 胶内酶解后行肽指纹图分析及网上数据库检索, 鉴定差异蛋白质;应用Western印迹法检测部分差异蛋白的表达情况。结果: 建立了化疗高敏感组和化疗低敏感组的双向凝胶电泳图谱, 多数蛋白质点集中于pH 4~8、相对分子质量为(20~100)×103。高敏感组和低敏感组的电泳图谱中平均蛋白质点数分别为(842±23)个和(793±19)个, 2组平均匹配率为90.7%, 2组间差异表达蛋白质点数为(79.00±13.56)个;选择30个差异蛋白质点进行质谱分析, 经数据库查询鉴定出9个差异表达蛋白。结论: 在化疗敏感性不同的结直肠癌中存在蛋白质表达的差异, 这些差异表达蛋白可能与化疗敏感性有关, 并可能用于化疗敏感性的预测。
标    签 结直肠肿瘤   蛋白质组学   药物耐受性   电泳, 凝胶, 双向   Colorectal neoplasms   Proteomics   Drug tolerance   Electrophoresis,gel,two-dimensional  
 
Abstract
Objective: The study aims to screen chemosensitivity-associated proteins in colorectal carcinoma tissues by using two-dimensional gel electrophoresis(2-DE) and mass spectrometry,then identify some differentially-expressed proteins. Methods: The patients with advanced colorectal carcinoma were confirmed by clinical diagnosis. Fresh carcinoma specimens were collected by biopsy and preserved in liquid N2. The tissues were classified into two groups: high sensitivity group(HS) and low sensitivity group(LS) based on drug sensitivity test. The total proteins were extracted and separated by 2-DE. The images were composed, compared, and differentially analyzed to identify the proteins with differential expression in HS and LS groups. Then the differentially-expressed protein spots were incised from the gels and digested by trypsin. The peptide mass fingerprintings(PMF) was acquired after matrix assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF-MS) and the proteins were identified by data searching in the Mascot database. Two proteins with differential expression were detected by Western blotting.Results: The 2-DE spectrum of HS and LS groups were established. Most protein spots were distributed in the area with pH 4-8 and relative molecular weight of(20-100)×103. The average number of the protein spots was 842±23 in HS group and 793±19 in LS group,respectively. The mean matching rate was 90.7%. The number of differentially-expressed dots between HS and LS group was 79.00±13.56. Thirty protein dots were selected for mass spectrum and bioinformatic analysis, and 9 proteins were identified. Conclusion: Colorectal carcinoma with different chemosensitivity had differential protein expression profiles. The differentially expressed proteins may be associated with chemosensitivity and could be used for prediction of chemosensitivity of colorectal carcinoma.

中图分类号 R735.5   DOI 10.3781/j.issn.1000-7431.2010.02.007

 
  购买该论文  中国光学期刊网论文下载说明
      


所属栏目 临床研究

基金项目 湖南省卫生厅科研基金资助课题(编号: C2005-009); 湖南省科学技术厅科技计划项目(编号: 05SK3007)

收稿日期 2009/7/31

修改稿日期 2009/9/21

网络出版日期

作者单位点击查看


引用该论文: ZHU Hong,PEI Hai-ping,LI Yi-xiong,YI Qiong,CAO Hui. Proteomic identification of chemosensitivity-associated proteins in human colorectal carcinomas[J]. Tumor, 2010, 30(2): 119~124
朱红,裴海平,李宜雄,易琼,曹慧. 结直肠癌化疗敏感性相关蛋白的蛋白质组学初步研究[J]. 肿瘤, 2010, 30(2): 119~124


论文评价
共有人对该论文发表了看法,其中:
人认为该论文很差
人认为该论文较差
人认为该论文一般
人认为该论文较好
人认为该论文很好
分享论文
分享到新浪微博 分享到腾讯微博 分享到人人网 分享到 Google Reader 分享到百度搜藏分享到Twitter

参考文献
【1】陈主初,梁宋平. 肿瘤蛋白质组学[M]. 长沙:湖南科学技术出版社,2002:33-34.
 
【2】CARR K M, ROSENBLATT K, PETRICOIN E F, et al. Genomic and proteomic approaches for studying human cancer:prospects for true patient-tailored therapy[J].Hum Genomics, 2004, 1(2):134-140.
 
【3】黄龙, 秦环龙. 蛋白组学技术分析不同转移潜能结肠癌细胞株差异表达蛋白[J].肿瘤,2008,28(11):925-928.
 
【4】彭佳远,张清福,秦环龙.结肠癌发生和发展不同阶段的差异蛋白质组学实验研究[J].肿瘤,2008,28(12):1023-1028.
 
【5】PEI H, ZHU H, ZENG S, et al. Proteome analysis and tissue microarray for profiling protein markers associated with lymph node metastasis in colorectal cancer[J].J Proteome Res, 2007, 6(7):2495-2501.
 
【6】STIERUM R, GASPARI M, DOMMELS Y, et al.Proteome analysis reveals novel proteins associated with proliferation and differentiation of the colorectal cancer cell line Caco-2[J].Biochim Biophys Acta, 2003,1650(1/2):73-91.
 
【7】STULIK J, HEMYCHOVA L, PORKERTOVA S,et al.Proteome study of colorectal cancinogenesis[J].Electrophoresis,2001,22(14):3019-3025.
 
【8】YOSHIKAWA R, YANAGI H, HASHIMOTO-TAMAOKI T, et al. Gene expression in response to anti-tumour intervention by polysaccharide-K (PSK) in colorectal carcinoma cells[J].Oncol Rep J, 2004, 12(6):1287-1293.
 
【9】SOHN K J, SMIRNAKIS F, MOSKOVITZ D N, et al. Effects of folylpolyglutamate synthetase modulation on chemosensitivity of colon cancer cells to 5-fluorouracil and methotrexate[J].Gut, 2004, 53(12):1825-1831.
 
【10】DONG Y B, YANG H L, MCMASTERS K M. E2F-1 overexpression sensitizes colorectal cancer cells to camptothecin[J].Cancer Gene Ther, 2003, 10(3):168-178.
 
【11】GOUVERIS P, LAZARIS A C, PAPATHOMAS T G, et al. Topoisomerase Ⅰ protein expression in primary colorectal cancer and recurrences after 5-FU-based adjuvant chemotherapy[J].J Cancer Res Clin Oncol, 2007,133(12):1011-1015.
 
【12】KWON W S, RHA S Y, CHOI Y H, et al. Ribonucleotide reductase M1(RRM1) 2464G>A polymorphism shows an association with gemcitabine chemosensitivity in cancer cell lines[J].Pharmacogenet Genomics, 2006,16(6):429-438.
 
【13】BERGMAN A M, EIJK P P, RUIZ VAN HAPEREN V W, et al. In vivo induction of resistance to gemcitabine results in increased expression of ribonucleotide reductase subunit M1 as the major determinant[J].Cancer Res, 2005, 65(20):9510-6.
 
【14】OKUMURA K, MEKATA E, SHIOMI H, et al. Expression level of thymidylate synthase mRNA reflects 5-fluorouracil sensitivity with low dose and long duration in primary colorectal cancer[J].Cancer Chemother Pharmacol, 2008, 61(4):587-594.
 
【15】INOUE T, HIBI K, NAKAYAMA G, et al. Expression level of thymidylate synthase is a good predictor of chemosensitivity to 5-fluorouracil in colorectal cancer[J].J Gastroenterol, 2005,40(2):143-147.
 
【16】TANAKA Y, FUJIWARA K, TANAKA H, et al. Paclitaxel inhibits expression of heat shock protein 27 in ovarian and uterine cancer cells[J].Int J Gynecol Cancer, 2004, 14(4):616-620.
 
【17】MAZUROV V V, SOLOVIEVA M E, LESHCHENKO V V, et al. Small heat shock protein hsp27 as a possible mediator of intercellular adhesion-induced drug resistance in human larynx carcinoma HEp-2 cells[J]. Biosci Rep, 2003,23(4):187-197.
 
【18】CHAUHAN D, LI G, SHRINGARPURE R, et al. Blockade of HSP27 overcomes Bortezomib/proteasome inhibitor PS-341 resis-tance in lymphoma cells[J]. Cancer Res,2003, 63(19):6174-6177.
 
【19】HAN E K, TAHIR S K, CHERIAN S P, et al. Modulation of paclitaxel resistance by annexin Ⅳ in human cancer cell lines[J]. Br J Cancer, 2000, 83(1):83-88.
 
【20】MATHIEU A, REMMELINK M, D'HAENE N, et al. Development of a chemoresistant orthotopic human nonsmall cell lung carcinoma model in nude mice:analyses of tumor heterogenity in relation to the immunohistochemical levels of expression of cyclooxygenase-2, ornithine decarboxylase, lung-related resistance protein, prostaglandin E synthetase, and glutathione-S-transferase-alpha (GST)-alpha, GST-mu, and GST-pi[J]. Cancer, 2004, 101(8):1908-1918.
 
【21】ZHANG T, GUAN M, JIN H Y, et al. Reversal of multidrug resistance by small interfering double-stranded RNAs in ovarian cancer cells[J]. Gynecol Oncol, 2005, 97(2):501-507.
 
相关信息
   标题 相关频次
 结直肠癌奥沙利铂耐药相关蛋白的筛选与鉴定
 8
 放疗敏感性不同宫颈癌组织的蛋白质组学比较研究
 6
 蛋白组学技术分析不同转移潜能结肠癌细胞株差异表达蛋白
 4
 结肠癌发生和发展不同阶段的差异蛋白质组学实验研究
 4
 人肺腺癌细胞株A549和A549/DDP的比较蛋白质组学研究
 4
 GRIM-19基因对肺腺癌耐药细胞株A549/DDP药物敏感性及相关基因表达的影响
 2
 K-Ras基因突变型结直肠癌治疗的研究进展
 2
 MTHFRABCG2单核苷酸多态性对晚期结直肠癌一线化疗疗效的预测作用
 2
 SLC22A18基因对人胶质瘤U251细胞化疗药物敏感性的影响
 2
 UGT1A1*28基因多态性联合SN-38药代动力学检测在进展期结直肠癌以伊立替康为基础的二线治疗中的应用
 2
 UGT1A1*28基因多态性与晚期结直肠癌伊立替康化疗疗效及不良反应的关系
 2
 Ⅰ~Ⅲ期根治术后左右半结肠癌预后差异分析
 2
 5-氟尿嘧啶为基础的联合化疗对结直肠癌患者血糖代谢的影响
 2
 5-杂氮-2'-脱氧胞苷对人结直肠癌HCT116细胞KISS1基因表达及侵袭迁移的影响
 2
 AGE/RAGE参与结直肠癌细胞上皮-间质转化及肿瘤干性的调控
 2
 B7-H1和Bcl-2在人结直肠癌中表达及其临床意义
 2
 CBX2蛋白在结直肠癌中的表达水平及临床意义
 2
 EphB2蛋白在结直肠癌中的表达及意义
 2
 FOLFOX联合贝伐珠单抗或西妥昔单抗一线治疗野生型KRAS晚期结直肠癌的临床疗效
 2
 GPR48单克隆抗体的制备及其在结直肠癌中的表达
 2
 HER2及FOXM1在结直肠癌中的临床意义及相互关系的研究进展
 2
 hTERT和E2F-1蛋白在结直肠癌组织中的表达及其临床意义
 2
 MicroRNA在结直肠癌的诊断、预后和化疗中的作用
 2
 MiR-192对结直肠癌细胞ZEB2表达及迁移和侵袭的影响
 2
 MiR-214对人结肠癌HCT116细胞生物学功能的影响
 2
 miRNA-21表达水平与结直肠癌患者预后关系的Meta分析
 2
 MMP 9及E-cadherin在结直肠癌中的表达及意义
 2
 mTOR信号通路调控结直肠癌LoVo/ADR细胞多药耐药性的可能机制
 2
 PPFP基因转染人正常甲状腺细胞Nthy-ori 3-1前后的蛋白质组学研究
 2
 PRDX4蛋白在肾透明细胞癌中表达下调与恶性程度增高相关
 2

  热点专题


关于我们  |   联系我们  |   广告投放  |   《肿瘤》杂志社版权所有 《肿瘤》杂志社   © 中国 上海 2014.3
沪ICP备15036656号-2