鼻咽癌组织EGFR、HSP90A和组织蛋白酶D表达水平及其与肿瘤侵袭转移的关系分析
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摘要
目的探讨鼻咽癌组织表皮生长因子受体(EGFR)、热休克蛋白90A(HSP90A)和组织蛋白酶D(cathepsin D)表达水平及其与肿瘤侵袭转移的关系。方法选取2014年1月至2015年12月南华大学附属第一医院收治的58例鼻咽癌患者(A组),采用免疫组织化学法检测其活检鼻咽癌组织的EGFR、HSP90A和cathepsin D阳性表达率,并检测同期30例鼻中隔偏曲手术患者(B组)正常鼻甲黏膜组织的EGFR、HSP90A和cathepsin D阳性表达率。统计A组患者的肿瘤T分期、N分期及淋巴管密度(LVD)。比较A组鼻咽癌组织EGFR、HSP90A和cathepsin D表达阳性与阴性患者的T分期、N分期及LVD,并分析鼻咽癌组织EGFR、HSP90A和cathepsin D表达与T分期、N分期及LVD的关系。结果 A组EGFR、HSP90A和cathepsin D阳性表达率分别86.21%、82.76%和87.93%,均高于B组的30.00%、26.67%和33.33%(P<0.05)。A组EGFR、HSP90A、cathepsin D蛋白表达阳性患者T3~T4分期患者百分比、N2~N3分期患者百分比及LVD均高于相应蛋白表达阴性患者,差异均有统计学意义(P<0.05)。Spearman相关分析结果显示,鼻咽癌组织EGFR、HSP90A和cathepsin D阳性表达率与其T分期、N分期及LVD均呈正相关(EGFR:r=0.844、0.795、0.785;HSP90A:r=0.862、0.825、0.822;cathepsin D:r=0.842、0.815、0.863,P<0.05)。结论鼻咽癌组织EGFR、HSP90A和cathepsin D表达与肿瘤侵袭转移均密切相关,可能作为评估鼻咽癌侵袭转移的参考指标。
Objective To investigate the expressions of epidermal growth factor receptor(EGFR),heat shock protein 90 A(HSP90 A)and cathepsin D in nasopharyngeal carcinoma and their relationship with tumor invasion and metastasis.Methods From January 2014 to December 2015,58 patients with nasopharyngeal carcinoma(group A)in the First Affiliated Hospital of University of South China were selected,and the positive expression rates of EGFR,HSP90 Aand cathepsin D in biopsy specimens of nasopharyngeal carcinoma were detected by immunohistochemistry method.The positive expression rates of EGFR,HSP90 Aand cathepsin D in biopsy chronic rhinitis tissues of 30 patients with chronic rhinitis(group B)were also detected.T staging,N staging and lymphatic vessel density(LVD)of patients in group A were analyzed.In group A,the T staging,N staging and LVD of between patients with positive expression of EGFR,HSP90 Aand cathepsin D and those with negative expression of these indicators were compared,and the correlations of the expression of EGFR,HSP90 Aand cathepsin D to T staging,N staging and LVD were analyzed.Results The positive expression rates of EGFR,HSP90 Aand cathepsin D in group A were 86.21%,82.76% and 87.93%respectively,which were higher than 30.00%,26.67% and 33.33%in group B(P<0.05).In group A,the percentages of patients on T3-T4 and N2-N3 stages and LVD of patients with positive expression of EGFR,HSP90 Aand cathepsin D protein respectively were higher than those of patients with negative expression of corresponding protein(P <0.05).Spearman correlation analysis showed that the positive expression rates of EGFR,HSP90 Aand cathepsin D in nasopharyngeal carcinoma were positively correlated with the T staging,N staging and LVD(EGFR:r=0.844,0.795,0.785;HSP90 A:r=0.862,0.825,0.822;cathepsin D:r=0.842,0.815,0.863,P<0.05).Conclusion EGFR,HSP90 Aand cathepsin D expression in nasopharyngeal carcinoma are closely related to invasion and metastasis of tumor,which may be used as reference indexes for the evaluation of tumor invasion and metastasis in nasopharyngeal carcinoma.
Objective To investigate the expressions of epidermal growth factor receptor(EGFR),heat shock protein 90 A(HSP90 A)and cathepsin D in nasopharyngeal carcinoma and their relationship with tumor invasion and metastasis.Methods From January 2014 to December 2015,58 patients with nasopharyngeal carcinoma(group A)in the First Affiliated Hospital of University of South China were selected,and the positive expression rates of EGFR,HSP90 Aand cathepsin D in biopsy specimens of nasopharyngeal carcinoma were detected by immunohistochemistry method.The positive expression rates of EGFR,HSP90 Aand cathepsin D in biopsy chronic rhinitis tissues of 30 patients with chronic rhinitis(group B)were also detected.T staging,N staging and lymphatic vessel density(LVD)of patients in group A were analyzed.In group A,the T staging,N staging and LVD of between patients with positive expression of EGFR,HSP90 Aand cathepsin D and those with negative expression of these indicators were compared,and the correlations of the expression of EGFR,HSP90 Aand cathepsin D to T staging,N staging and LVD were analyzed.Results The positive expression rates of EGFR,HSP90 Aand cathepsin D in group A were 86.21%,82.76% and 87.93%respectively,which were higher than 30.00%,26.67% and 33.33%in group B(P<0.05).In group A,the percentages of patients on T3-T4 and N2-N3 stages and LVD of patients with positive expression of EGFR,HSP90 Aand cathepsin D protein respectively were higher than those of patients with negative expression of corresponding protein(P <0.05).Spearman correlation analysis showed that the positive expression rates of EGFR,HSP90 Aand cathepsin D in nasopharyngeal carcinoma were positively correlated with the T staging,N staging and LVD(EGFR:r=0.844,0.795,0.785;HSP90 A:r=0.862,0.825,0.822;cathepsin D:r=0.842,0.815,0.863,P<0.05).Conclusion EGFR,HSP90 Aand cathepsin D expression in nasopharyngeal carcinoma are closely related to invasion and metastasis of tumor,which may be used as reference indexes for the evaluation of tumor invasion and metastasis in nasopharyngeal carcinoma.
引文
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[2]THOMPSON L D,PENNER C,HO N J,et al.Sinonasal tract and nasopharyngeal adenoid cystic carcinoma:a clinicopathologic and immunophenotypic study of 86cases[J].Head Neck Pathol,2014,8(1):88-109.
[3]CARPENTER B L,CHEN M,KNIFLEY T,et al.Integrinα6β4promotes autocrine epidermal growth factor receptor(EGFR)signaling to stimulate migration and invasion toward hepatocyte growth factor(HGF)[J].J Biol Chem,2015,290(45):27228-27238.
[4]SNIGIREVA A V,VRUBLEVSKAYA V V,SKARGA Y Y,et al.Effect of heat shock protein 90(Hsp90)on migration and invasion of human cancer cells in vitro[J].Bull Exp Biol Med,2014,57(4):476-478.
[5]王园园,贺秋艳,易红梅,等.RKIP在鼻咽癌侵袭转移中的作用及机制研究[J].临床与病理杂志,2015,35(3):375-381.
[6]SANG Y,CHEN M Y,LUO D,et al.TEL2suppresses metastasis by down-regulating SERPINE1in nasopharyngeal carcinoma[J].Oncotarget,2015,6(30):29240-29253.
[7]POSCHAU M,DICKREUTER E,SINGH-MLLER J,et al.EGFR andβ1-integrin targeting differentially affect colorectal carcinoma cell radiosensitivity and invasion[J].Radiother Oncol,2015,116(3):510-516.
[8]DA ROSA M R,FALCO AS,FUZII H T,et al.EGFR signaling downstream of EGF regulates migration,invasion,and MMP secretion of immortalized cells derived from human ameloblastoma[J].Tumour Biol,2014,35(11):11107-11120.
[9]王亚飞.组织蛋白酶D在鼻咽癌细胞中相互作用蛋白的筛选与鉴定[D].衡阳:南华大学,2014.
[10]PRANJOL M Z,GUTOWSKI N,HANNEMANN M,et al.The potential role of the proteases cathepsin D and cathepsin L in the progression and metastasis of epithelial ovarian cancer[J].Biomolecules,2015,5(4):3260-3279.
[11]王亚飞.Cathepsin D与恶性肿瘤的关系[J].肿瘤基础与临床,2014,27(1):79-81.
[12]BACH A S,DEROCQ D,LAURENT-MATHA V,et al.Nuclear cathepsin D enhances TRPS1transcriptional repressor function to regulate cell cycle progression and transformation in human breast cancer cells[J].Oncotarget,2015,6(29):28084-28103.