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摘要: 目的:检测乙酰肝素酶(HPA)、蛋白激酶CK2β(CK2β)、缺氧诱导因子-1α(HIF-1α)在鼻咽癌(NPC)组织中的表达及其与临床特征之间的关系;并分析三者在NPC组织中表达的相关性。方法:采用免疫组织化学染色技术Super-Vision法检测49例NPC组织标本及15例慢性鼻咽炎(CNT)组织标本中HPA、CK2β及HIF-1α的表达水平。结果:HPA、CK2β与HIF-1α在NPC组织中的表达水平均高于CNT组织中的表达,差异均有统计学意义(P<0.05);HPA、CK2β与HIF-1α的表达与NPC临床分期、治疗后有无复发或转移相关(P<0.05),与患者的性别无关(P>0.05);HIF-1α的表达水平与NPC患者的年龄密切相关(P<0.01),而HPA、CK2β的表达水平则与NPC患者的年龄无关(P>0.05);HPA、CK2β与HIF-1α任意两者间在NPC组织中的表达均呈正相关性(P<0.05)。结论:HPA、CK2β和HIF-1α参与了NPC的发生和发展、浸润及转移;在NPC的发生发展过程中,HPA、CK2β和HIF-1α之间可能存在协同作用。Abstract: Objective:To investigate the expression of HPA,CK2β and HIF-1α gene in nasopharyngeal carcinoma(NPC) tissues, and the correlation between their expression with the clinical characteristics of NPC and the relativity of HPA,CK2β and HIF-1α gene in NPC tissues.Method:HPA, CK2β and HIF-1α were detected with Super-Vision immunohistochemical method using antibody in 49 NPC specimens and 30 specimens with chronic nasopharyngitis tissue(CNT).Result:The expression of HPA,CK2β and HIF-1α in NPC tissue were significantly higher than those in CNT tissue (P<0.05,separately). The expression of HPA,CK2β and HIF-1α were significantly related to the TNM stage and whether recurrence or metastasis occur after treatment (P<0.05,separately), but there was no obvious correlation between its expression and the sex of NPC patient(P>0.05). The expression of HIF-1α was significantly related to the age of NPC patient (P<0.05), while HPA,CK2β were not. The expression of HPA,CK2β and HIF-1α in NPC tissue was positively correlated with each other (P<0.05, separately).Conclusion:HPA, CK2β and HIF-1α play synergetic role in development of NPC, which plays an important role in invasiveness,recurrence and metastasis of NPC. There could be a positive cooperation among HPA, CK2β and HIF-1α in the carcinogenesis and development of NPC.
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Key words:
- nasopharyngeal neoplasm /
- heparanase /
- protein kinase CK2β /
- hypoxia inducible factor-1α
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[1] SUN W, ZHOU S, CHANG S S, et al.Mitochondrial mutations contribute to HIF1 alpha accumulation via increased reactive oxygen species and up-regulated pyruvate dehydrogenease kinase 2in head and neck squamous cell carcinoma[J].Clin Cancer Res, 2009, 15:476-484.
[2] 吴蕾, 刘邦华.蛋白激酶CK2在喉正常组织及喉癌前病变和喉癌中的表达及意义[J].临床耳鼻咽喉头颈外科杂志, 2007, 21 (18):825-830.
[3] BECKHOVE P, HELMKE B M, ZIOUTA Y, et al.Heparanase expression at the invasion front of human head and neck cancers and correlation with poor prognosis[J].Clin Cancer Res, 2005, 11:2899-2906.
[4] COHEN-KAPLAN V, NARODITSKY I, ZETSER A, et al.Heparanase induces VEGF C and facilitates tumor lymphangiogenesis[J].Int J Cancer, 2008, 123:2566-2573.
[5] CHEN G, DANG Y W, LUO D Z, et al.Expression of heparanase in hepatocellular carcinoma has prognostic significance:a tissue microarray study[J].Oncol Res, 2008, 17:183-189.
[6] COHEN I, PAPPO O, ELKIN M, et al.Heparanase promotes growth, angiogenesis and survival of primary breast tumors[J].Int J Cancer, 2006, 118:1609-1617.
[7] DAVIDSON B, SHAFAT I, RISBERG B, et al.Heparanase expression correlates with poor survival in metastatic ovarian carcinoma[J].Gynecol Oncol, 2007, 104:311-319.
[8] COHEN-KAPLAN V, DOWECK I, NARODITSKY I, et al.Heparanase augments epidermal growth factor receptor phosphorylation:correlation with head and neck tumor progression[J].Cancer Res, 2008, 68:10077-10085.
[9] GIUSIANO S, COCHET C, FILHOL O, et al.Protein kinase CK2 alpha subunit over-expression correlates with metastatic risk in breast carcinomas:quantitative immunohistochemistry in tissue microarrays[J].Eur J Cancer, 2011, 47:792-801.
[10] HUNG M S, LIN Y C, MAO J H, et al.Functional polymorphism of the CK2 alpha intronless gene plays oncogenic roles in lung cancer[J].PLoS One, 2010, 5:e11418.
[11] 刘新光, 阮杰, 梁念慈.蛋白激酶CK2βsiRNA对肺腺癌细胞A549增殖的抑制作用[J].中国肿瘤临床, 2009, 36 (12):701-706.
[12] CARO J.Hypoxia regulation of gene transcription[J].High Alt Med Biol, 2001, 2:145-154.
[13] WENGER R H, STIEHL D P, CAMENISCH G.Integration of oxygen signaling at the consensus HRE[J].Sci STKE, 2005, 2005:re12.
[14] 祁玉娟, 李积德, 赵君慧, 等.c-myc、HIF-1α和VEGF在高海拔地区乳腺癌的表达及临床意义[J].实用肿瘤杂志, 2010, 25 (1):32-36.
[15] 胡建莉, 陈萍, 刘伟, 等.食管鳞癌中VEGF_(165b)、HIF-1α的表达及临床意义[J].肿瘤防治研究, 2010, 37 (1):9-11.
[16] 莫立根, 罗元, 邝国乾, 等.HIF-1α在鼻咽癌组织中表达及意义[J].现代肿瘤医学, 2007, 15 (1):19-21.
[17] HE X, BRENCHLEY P E, JAYSON G C, et al.Hypoxia increases heparanase-dependent tumor cell invasion, which can be inhibited by antiheparanase antibodies[J].Cancer Res, 2004, 64:3928-3933.
[18] 马建刚, 路秀英, 李晓明.低氧对人喉癌Hep-2细胞乙酰肝素酶蛋白表达及其侵袭力的影响[J].中华耳鼻咽喉头颈外科杂志, 2006, 41 (3):216-219.
[19] 刘嘉琳, 张颖, 吴艳萍, 等.乙酰肝素酶、缺氧诱导因子-1α的表达与食管鳞癌浸润转移的关系[J].军事医学科学院院刊, 2007, 31 (2):133-136.
[20] 姚俊, 赵杰刚, 王新帅, 等.乙酰肝素酶和低氧诱导因子1α在胆管癌中的表达及其临床意义[J].西安交通大学学报 (医学版), 2011, 32 (1):111-113.
[21] 张磊, 张煦, 杨爱军, 等.胃癌组织中HPA和HIF-1α的表达及意义[J].山东医药, 2009, 49 (2):89-90.
[22] RICHARD D E, BERRA E, GOTHIE E, et al.p42/p44 mitogen-activated protein kinases phosphorylate hypoxia-inducible factor 1alpha (HIF-1alpha) and enhance the transcriptional activity of HIF-1[J].J Biol Chem, 1999, 274:32631-32637.
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