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胃癌组织中PDCD5、COX-2和CD44的表达及其临床意义
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摘要
目的:通过检测PDCD5、COX-2和CD44在胃癌、胃炎和正常胃粘膜组织中的表达,分析PDCD5、COX-2和CD44的表达及与临床病理因素的相关性,探讨其在胃癌发生发展中的作用,为胃癌的诊断和判断预后提供一种理想的肿瘤标记物。同时探讨胃癌组织中PDCD5、COX-2和CD44三者表达的相关性。
     方法:选取我院2003-2004年间手术切除并经病理证实、资料完整的32例胃癌组织标本、16例胃炎组织标本和12例正常胃粘膜组织标本的存档蜡块,应用组织芯片技术,通过免疫组化SABC法进行PDCD5、COX-2和CD44的检测,并对三者的表达情况及与胃癌临床病理特征的关系、三者在胃癌组织中表达的相关性进行统计分析。
     结果:与胃炎和正常胃粘膜组织相比,在胃癌组织中COX-2和CD44的表达明显升高(P<0.05),而PDCD5的表达明显降低(P<0.05);COX-2与胃癌细胞的侵润及淋巴结转移呈明显相关(P<0.05),但与胃癌组织分化程度及临床分期无相关性(P>0.05),而CD44与胃癌淋巴结转移、临床分期和侵润深度呈明显相关(P<0.05),但与胃癌的分化程度无相关性(P>0.05),三者的阳性表达与胃癌的部分恶性生物学行为有关。在有随访结果的32例胃癌患者中,生存分析显示,淋巴转移、临床分期、PDCD5、CD44及COX-2的表达均与预后有关(P<0.05),胃癌组织分化与预后无关(P>0.05)。
     结论:COX-2、CD44在胃癌组织中过量表达伴随PDCD5表达缺失,与胃癌转移和侵润密切相关,三者可能存在共同的转录激活机制,构成了胃癌发生的多种途径,联合检测3种基因能更准确判断胃癌转移和侵润状态。
Objective The purpose of study was to explore the expression of PDCD5、COX-2 and CD44 in gastric cancer and chronic gastritis tissues,The expression of them was also detected in normal gastric tissues.With analysis of the relationships between the expression of PDCD5、COX-2 and CD44 and degrees of difrer-entiation,lymph node metastases and Borrmann stages.To investigate its possible mechanisms in the development and progression of gastric cancer.Aiming to find ideal tumor marker for diagnosis and prognosis.At the same time the correlation of expression of PDCD5、COX-2 and CD44 was explored.
     Methods Using tissue microarray technique,in 32 stomach carcinoma tissues、16 chronic gastritis tissues and 12 normal gastric tissues,the expression of PDCD5、COX-2 and CD44 were examined by using streptavidin-biotin-peroxidase complex technique (SABC) method.All of the tissues were fixed in neutral formallin and enbedded in paraffin collected from 2003 to 2004.The correlation among these three genes was analyzed.
     Results The expression levels of COX-2 and CD44 were upregulated (P<0.05),while the expression of PDCD5 downregulated(P<0.05) in gastric carcinoma compared with non-tumor tissues;the over-expression of COX-2 in gastric cancer was positively related to the metastasis and the depth of invasion (P<0.05),while it was not related with the histological types (P>0.05),and Borrmann types (P>0.05);the over-expression of CD44 in gastric cancer was obviously related to the metastasis、Borrmann types and the depth of invasion (P<0.05),while it was not related with the histological types (P>0.05), Upregulating expression levels of PDCD5 and CD44 were significance correlated with some malignant behaviour of gastric cancer.In the 32 cases with followed-up data,survi-val analysis reveal that the survival was correlated with invading of the metastasis Borrmann types and the expression of PDCD5、COX-2 and CD44.The histological grades were not related to prognosis.
     Conclusion Patients who had over expression of COX-2 and CD44 and low expressi-on of PDCD5 have a higher invasion of tumor and lymph metastatic rate,it was speculated that may be a congenerous transcription mechanism with which to construct multiple pathways contributing to the development and progression of gastric cancer. Combined detection of three genes is a reliable index to evaluate the invasion and metastasis of gastric carcinoma.
引文
[1]Han CB,Mao XY,Xin Y,et al.Quantitative analysis of tumor mitochondrial RNA using microarray, World J Gastroenterol,2005,11:36-40.
    [2]Han CB, Ma JM, Xin Y,etal.Mutations of mitochondrial 12S Rrna IN Gastric carcinoma and their significance World J Gastroenterol,2005,11:31-35.
    [3]刘勇,路生芝.生物芯片技术及其在肿瘤研究中的应用.江西医学检验,2002,20:376-378.
    [4]Li H, Sun Y, Kong QY, et al. Combination of nucleic acid and protein isolation with tissue array construction:using defined histologic regions in single frozen tissue blocks for multiple research purposes. Int J Med,2003,12:299-304.
    [5]Cui DX, Zhang L, Yan XJ, et al. A microarray-based gastric carcinoma prewaning system. World J Gastroenterol,2005,11:1273-1282.
    [6]Dan HL, Zhang YL, Zhang Y,et al. A novel method for preparation of tissue-microarray. World J Gastroenterol,2004,10:579-582.
    [7]Lusis EA, Chicoine MR, Perry A. High throughputscreening of meningioma biomarkers using a tissue xnicroarray.J Neurooncol,2005,73:219-223.
    [8]Sun Y, Li JY, He JS, et al.Tissue microarray analysis of multiple gene expression in intestinal metaplasia, dysplasia and carcinoma of the stomach. Histopathology,2005, 46:505-514.
    [9]Green DR.Apoptotic pathways:paper wraps stone blunts scissors. [J].Cell,2000; 102(1):1-4.
    [10]Hellin AC,Bentires-Alj M,Verlaet M,et al Roles of Nuclear Factor-kappaB,p53, and p21/WAF1 in Daunomycin-Induced Cell Cycle Arrest and Apoptosis.[J].Pharmacol ExpTher.2000; 295 (3):870-878.
    [11]Liu HT, Wang YG,Zhang YM, et al. PDCD5, a novel apoptosis related gene cloned from human leukemia cell line TF-1,could enhanceapoptosis of some tumor cells induced by growth factor withdrawal.Biochem Biophy Res Comm,1999,254:203-210.
    [12]Yang YH,Zhao M,Li WM,et al.Expression of programmed cell death 5 gene involves in regulation of apoptosis in gastric tumor cells. Apoptosis,2006,11(6):993-1001.
    [13]Wu AW,Gu J,Li ZF,et al.COX-2 expression and tumor angiogenesis in colorectal cancer.World J Gastroentrol.2004,10:2323-2326.
    [14]Hutchison R. COX-2-selective NSAIDs.Am J Nurs,2004,104:52-55.
    [15]Evans JF,Kargman SL.Cancer and cycloxygenase-2(COX-2) inhibition.Curr Ph-arm Des,2004,10:627-634.
    [16]Mohammed NA,Abd El-Aleem SA,E1-Hafiz HA,et al.Distribution of constitutive and inducible cycloxygenase-2(COX-2) in postviral human liver cirrhosis:a possible role for COX-2 in the pathogenesis of liver cirrhosis J Clin Pathol,2004,57:350-354.
    [17]Singh B,Berry JA,Shoher A,et al. COX-2 overexpression increases motility and invasion of breast cancer cells.Int J Oncol 2005,26:1393-1399.
    [18]Eibl G,Takata Y,Boros LG,etal.Growth stimulation of COX-2-negative pancreative cancer by a selective COX-2 inhibitor.Cancer Res,2005,65:982-990.
    [19]Shiotani H,Denda A,Yamamoto K,et al.Increased expression of cyclooxygenase-2 protein in 4-nitroquinoline-oxide-induced rat tongue carcinomas and chemo preventive efficacy of aspecfic inhibitor, nimesulide[J].Cancer Res,2001,61(4):1451-1456.
    [20]Yazawa K,Tsuno NH,Kitayama J,et al,Selective inhibition of cyclooxygenase-2 inhibits colon cancer cell adhesion to extracellular matrix by decreased expression of betal integrin.Cancer Sci,2005,96:93-99.
    [21]Murata H,Kawano S,Tsuji S,et alcycloxygenase-2 overexpression enhances lymphatic invasion and metastasis in human gastric carcinoma. Am J Gastroentrol,1999, 94:451-455.
    [22]Ohno R,Mguchi Y, Toge T,et al.A dose-escalation and pharmacokinetic study of subcutaneously administered recombinant human interleukin 12 and its biological effects in Japanese patients with advanced malignancies.Clin Cancer Res,2000,6(7):2661-2669.
    [23]Tahara E.Genetic pathways of two types of gastric cancer.IARC Sci Pub,2004, (157):327-349.
    [24]丁友成,赵中辛,王理伟,等.CD44分子对胃癌细胞腹膜种植影响的体外实验研究[J].肿瘤,2005,25(5):450-452.
    [25]Lee MA,Hong YS,Kang JH,et al.Detection of Epstein Barrvirus by PCR and expression of LMP1,p53,CD44 ingastric cancer [J]. Korean J Intern Med,2004,19(1): 43-47.
    [26]Chen JQ,Zhan WH,He YL,etal.Expression of heparanase gene,CD44v6,MMP-7 and nm23 protein and their relationship with the invasion and metastasis of gastric carcinomas[J].World J Gastroenterol,2004,10(6):776-82.
    [27]Lesley J.CD44 and its interaction with extracel lularmatrix. Adv Immunol,1999, 54(4):271-276.
    [28]曲群,宗璐,杨整哉.CD44V6,CD44V78在宫颈癌中的表达.第四军医大学学报,2003,24(16):1500-1503.
    [29]Dong WQSun XM,Yu BP,et al.Role of VEGF and CD44v6 in differentiating benign from malignant ascites [J].World J Gas troenterol,2003,9(11):2596-600.
    [30]Yan X,Yanping W,Sumin Z,et al.Relationship between CD44v6 expression and metastatic potential and prognosisin gastric carcinoma [J].Chin Med Sci J,2000, 15(2):128.
    [31]Joo M,Lee HK,Kang YK.Expression of Ecadherin,betacatenin,CD44s and CD44v6 in gastric adenocarcinoma:relationship with lymphnode metastasis [J]. Anti cancer Res,2003,23(2B):1581-1588.
    [32]Lee HS,Lee HK,Kim HS,et al.Tumour suppress or gene expression correlates with gastric cancer prognosis.J Pathol,2003,200(1):39-46.
    [1]Litta LA,Steeg PS,Stetler-Steveson WG..Cancer metastasis and angiogenesis: anim-balance of positive and negative regulation[J].Cell,1991,64:327.
    [2]Zha S,Yegnasubramanian V,Nelson WQet al.Cyclooxyg-enasesincancer:progress and perspective[J].CancerLett,2004,215(1):1-20.
    [3]Ranger GS,Thomas V,Jewell A,et al.Elevated cyclooxygenase-2 expression correlates with distant metastases in breast cancer [J].Anticancer Res,2004,24(4):2349-2351.
    [4]Walker M. Eur Gastroenterol Hepatol,2002;14:347-349.
    [5]Sung jj,Leung WK,Go MY,et al Am J Pathol,2000; 157:729-735.
    [6]YoshimuraR,SanoH,MasudaC,et al.2000;89:589-596.
    [7]Dannenberg AJ,Altorki NK,BoyleJO,et al.Oncol,2001;2:544-551.
    [8]Howe LR, Dannenberg AJ.Semin.Oncol,2002;29:111-119.
    [9]Xu M, Cheng N, Gui L, et al.The 5'-upstream region of human programmed cell death 5 gene contains a highly active TATA-less promoter that is up-regulated by etop oside.Gene,2004,329:39-49.
    [10]GuoYJ,Liu QWang X,et al.Potential use of soluble CD44 inserumas indicator of Tumor burden and metastasis in patients with gastric or colon cancer[J]. Cancer Res, 1994,54(2):422
    [11]Ham HJ,Ho LI,Shyu RY,et al.Soluble CD44 is forms inserumas potential markers of metastatic gastric carcinoma[J].ClinGastroenterol,1996,22(2):107.
    [12]Mayer B,Jauch KW,Gunthert U,et al.De-novoexpression of CD44 and survivalin Gastric cancer[J].Lancet,1993,342(8878):1019.
    [13]Harn HJ,Ho LI,Chang JY,et al.Differential expression of the human metastasis adhe-Sion molecule CD44 vinnormal and carcinomatous stomach mucosa of Chinese subjects[J].Cancer,1995,75(5):1065.
    [14]Heider KH,Dammrich J,Skroch-Angel P,et al.Differential expression of CD44 splicEvariants in intestinal and diffusetype human gastric carcinoma and normal gastric mucosa [J].CancerRes,1993,53(18):4197.
    [15]Dammrich J,Vollmers HP,Heider KH,et al.Importance of different CD44v6 expression In human gastric intestinaland diffusetype cancers for metastatic lymphogen- ic spreading[J].Mol Med,1995,73(8):395.
    [16]Kim YS,Chi SG,Kim YW,et al.Molecular genetic characterization of alternatively spliced CD44 transcripts in human stomach carcinoma[J].JKorean MedSci,1997,12(6): 505.
    [17]Muller W,Schneiders A,Heider KH,et al.Expression and prognostic value of the CD44 splic in gvariants v5 and v6 in gastric cancer[J].Pathol,1997,183(2):222.
    [18]Yokozaki H,Ito R,Nakayama H,et al.Expression of CD44 abnormal transcripts in human gastriccarcinomas[J].CancerLett,1994,83(1-2):229.
    [19]Hong RL,Lee WJ,Shun CT,et al.Expression of CD44 and its clinical implication Indiffusetype and intestinal-type gastrica denocarcinomas[J].Oncology,1995,52(4):334.
    [20]刘鹏飞,吴孟超,陈汉,等.CD44剪接变异体在早期肝癌的表达及其临床意义[J].肿瘤,1996,16(9):532.
    [21]Uefuji K,Ichikura T,Mochizuki H,et al.Expression of clclooxygenase-2protein in gastric adenocarcinoma[J].Surg ONcol,1998,69(3):167-172.
    [22]Romano M,Riui V,Memoli A,et al. Helicobactor.pylori.upregulates. cyclooxygen-ase-2mRNA expression and prostagland in E2 synthesis in MKN28 gastric mucosal cell sinvitro[J].Biol Chem,1998,273(44):28560-28563.
    [23]LimHY,JooHJ,ChoiJH,et al.Clin Canres,2000,6(2):519-525.
    [24]Yu J,Leung WK,Ebert mpa,ET AL Br Jcancer,2002; 157:729-735.
    [25]Uefuji K,Ickikura T, Mochizuki H,et al.Clin Cancer Res,2000;6:135-138.
    [26]McCarthy CJ,Corofford LJ,Greenson J,et al.Cyclooxygenase-2 expression in gastric antral mucosa beforeand after eradication of helicobacter pylori infection [J].Am J Gastroenterol,1999,94:1218-1223.
    [27]Fu S,Ramanujam KS,Wong A,et al.increased expressionand cellular localization of inducible nitric oxide synthase and cyclooxygenase-2 in helicobacter pylori gastritis [J].Gastroenterology,1999,116:1319-1329.
    [28]Romano M,Ricci V,Memoli A,et al.Helicobacter pylori up-regu lates cyclooxyg-enase-2 mrna expression and prostaglandin E2.synthesis in MKN 28 gastric mucosal cells in vitro [J].Biol Chem,1998,273(4):28560-28563.
    [29]Yang YH, Zhao M, Li WM, et al. Expression of programmed cell death 5 gene involves in regulation of apop-to sis in gastric tumor cells. Apoptosis,2,006,11(6):993-1001.
    [30]KawabeA,ShimadaY,UchidaS,et al Expression of cyclooxygenase-2 in primary and remnant gastric carcinoma:comparing it with p53 accumulation,helicobacter pylori infection and vascular endothelial growth factor expression[j].J-Surg-Oncol,2002, 80(2):79.
    [31]Leung WK,Bai AH,Chan VY,ey al.Effect of peroxisome proliferate or activated receptor gammaligandson growth and gene expression profiles of gastric cancer cells[J].Gut,2004,53(3):331.
    [32]Joo YE,Rew JS,Seo YH,et al.Cyclooxygenase-2 over expression on correlates with vascular endothelial growth factor expression and tumor" angiogenesisin gastric cancer [J].J-Clin-Gastroenterol,2003,37(1):28.
    [33]Yu HQ,Li JY,Yang YN,et al.Increased abundance of cyclooxygenase-2 correlates with vascular endothelial growth factor-a abundance and tumor or angiogenesisin gastric cancer[J].Cancer-Lett,2003,195(1):43.
    [34]Jeffrey P,Walterschheid SE.Platelet-activating factor a molecular sensor for cellular damage activate systemic immune suppression. EXP Med,2002,195:171-179.
    [35]Duff MA,Stapeton P,Mstre JR,et al.cyclooxygenase-2 inhibition the antineo plasticactivity of interferon.Ann Surg Oncol,2003,10(3):305-313.
    [36]荆雪宁.CD44与肿瘤的免疫逃逸.国外医学肿瘤学分册,2004:186-189.
    [37]Marhaba R,Bourouba M,Zooler M.CD44V7 interferes with activation induced cell Deathby upregulation of antiapoptotic gene expression. Leukoc Biol 2003,74(1): 135-148.
    [38]Fujita Y,Kitagawa M,Nakamura S,et al.cd44 signaling through focal adhesion kinase andits antiapoptotic effect.FEBS Lett,2002,52(8):101-108.
    [39]Yasuda M,Tanaka Y,Fujii K,et al.cd44 stimulation downregulates Fas expression and Fas mediated apotosis of lung cancer cells.Int Immunol,2001,13:1309-1319.
    [40]李祖国,丁彦青,邓永健,等。CD44v6在大肠癌转移中的作用机理的研究[J].中华医学杂志,1998,78(10):729.
    [41]Ceccorii D, Scarpa A, Donadelli M, et al. Proteomic profiling of pancreatic ductal carcinoma cell lines treated with trichostatin-A.Electrophoresis.2003,24(11):1871- 1878.
    [45]Ji X, Cheung R, Cooper S, et al.Interferon alfa regulated gene expression in patients initiating interferon treat-ment for chronic hepatitis C.Hepatology,2003,37(3): 610-621.
    [46]Renzi MJ, Farrell FX, Bittner A, et al.Erythropoietin induces changes in gene expression in PC-12 cells.Brain Res Mol Brain Res,2002,104(1):86-95.
    [47]Wang Y, Li D, Fan H, et al.Cellular uptake of exogenous human PDCD5 protein J Biol Chem,2006,281 (34):24803-24817.
    [48]Rui M, Chen Y, Zhang Y, et al. Transfer of anti-TFAR19 monoclonal antibody in-to HeLa cells by in situ electroporation can inhibit the apoptosis. Life Sci 2002,71(15): 1771-1778.
    [49]田辉凯,夏天,蒋春笋,等TFAR19促进小鼠肝线粒体膜通透性转运孔的开放.生物化学与生物物理学报,2002,34(3):279-284.
    [50]杜颖,洪天配.TF-1细胞凋亡相关基因19与甲状腺肿瘤之间关系的初步探讨.中华内科杂志,2003,42(7):492-494.
    [51]宋清华,陈英玉,狄春晖,等TFAR19蛋白在系统性红斑狼疮患者血清中水平的检测.中华风湿学杂志,2003,7(9):563—565.
    [1]杨军,等组织芯片技术的发展及应用[J].中国实验诊断学,2003,7(3):195-198.
    [2]Kononen J, Bubendorf L, Kallioniemi OP,et al. Tissuemicroarrays for high through-put molecular profiling of tumor specimen [J].NatMed,1998,4(7):844-847.
    [3]Shergill IS,Shergill NK,Arya M,et al.Tissuemicroarrays:a current medical research tool.Curr Med Res Opin,2004,20:707-712.
    [4]Moch H,Lononen J,Kallioniemi OP, et al. Tissue microarray:what willthey bring to molecular and anatomic pathology [J].Advan Anato Pathol,2001,8(1):14-29.
    [5]Gulmann C, Grady A.Tissuemicroarrays:anoverview[J].Cur Diag Pathol,2003,9(3): 149-154.
    [6]刘勇,路名芝,袁晟.采用组织芯片技术检测胃癌组织中泛素、S相激酶相关蛋白2、p27的表达[J].中华消化杂志,2004,24(1):57-58.
    [7]Yoo NJ, Kim HS, Kim SY,et al. Stomach cancer highly expresses both initiator and effector caspases,immunohistochemical. study[J].APMIS,2002,11(11):825-832.
    [8]Park SY, Kim HS, Hong EK,et al.Expressionocytokeratins7 and 20 in primary carcinomas of the tomachs and colorectum and their value in the differential diagnosis of metastatic carcinoma stotheovary[J].HumPathol,2002,33(11):1078-1085.
    [9]Yoo NJ,Lee JW,Kim YJ,et al.Loss of caspase-2> 6 and 7 expression in gastric cancer.APMIS,2004,112:330-335
    [10]Lee SH, Lee JW, Kim HS,etal immunchistochemical analysis of OmiHtA2 expression in stomach cancer.APMIS,2003,111:586-590.
    [11]Lee SH,Kim HS,Kim SY,et al.Increased expression of FILP,an inhibitor of. Fas-mediated apoptosis in stomach cancer.APMIS,2003,111:309-314.
    [12]Tang Z,Zhao M, Ji J,etal.Overexpression of gastrin and c-met protein involved in human gastric carcinomas and intestinal metaplasia. Oncol Rep,2004,11:333-339.
    [13]Sheehan KM, Sabah M,Cummins RJ,et al. Cyclooxygenase-2 expression in stromal tumors of the gastrointestinal tract. Hum Pathol,2003,34:1242-1246.
    [14]Hao X,Sun B,Hu L,et al.Differential gene and protein expression in primary breast malignancies and their lymph node metastases as revealed by combined cDNA micr-oarray and tissuemicroarray analysis[J].Cancer,2004,100(6):1110-1122.
    [15]Maitra A, Hansel DE, Argani P, etal. Global expression analysis of well-differen-tiated pancreatic endocrine neoplasms using oligonucleotide microarrarys.Clin Cancer Res,2003,9(16pt1):5988-5995.

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