Ezrin和RhoA蛋白在鼻咽癌组织中的表达及临床意义
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摘要
目的：检测Ezrin和RhoA蛋白各自在不同临床分期鼻咽癌(Nasopharyngeal Carcinoma, NPC)组织中的表达,探讨二者在NPC发生和发展中的作用以及它们在其中的相互关系。为NPC浸润转移的机制提供新的理论依据。为NPC的早期诊断、临床防治及预后判断提供新的有价值的指标。
方法：
1.选取有完整临床资料及随访资料的150例NPC病例石蜡包埋组织标本作为实验组,选取20例鼻咽粘膜慢性炎石蜡包埋组织作为对照。
2.应用免疫组化Supervision二步法分别检测NPC和对照组组织中Ezrin和RhoA蛋白的表达情况。
3.采用SPSS13.0统计软件进行数据处理。用x2检验、Spearman等级相关分析法分析Ezrin和RhoA蛋白表达与NPC患者临床病理特征之间的关系；用Kaplan-Meier法进行单因素生存分析,log-rank法进行样本间生存率曲线差异检验。
结果：
1. Ezrin与RhoA蛋白在NPC组织中的阳性表达率分别为74.7%和62.7%,在对照组组织中基本不表达。两组差异都有非常显著统计学意义(均为P 2. Ezrin与RhoA蛋白阳性表达率在NPC临床TNM分期的T1、T2、T3、T4分别为：29.4%、65.5%、92.3%、88.5%和17.6%、52.7%、78.8%、80.8%,除T3与T4期,各T分期之间比较均有显著或非常显著统计学意义(P<0.05或P<0.001)；在N0、N1、N2、N3分别为53.8%、71.4%、79.6%、87.9%和46.2%、54.8%、65.3%、81.8%,Ezrin蛋白表达在N0与N2,N0与N3分期之间有显著差异(P<0.05),RhoA蛋白表达在N0与N1,N0与N3以及N1与N3分期之间有显著差异(P<0.05)；在M0与M1分别为72.5%、94.7%和60.3%、84.2%, M0与M1之间比较均有显著统计学意义(均为P<0.05)。
3. Ezrin与RhoA蛋白阳性表达率在临床分期Ⅰ、Ⅱ、Ⅲ、Ⅳ期中分别为50%、40%、80.7%、86.9%和0%、26.7%、64.9%、80.3%,两指标各期之间均有非常显著统计学意义(均为P<0.001)。
4.NPC组织中Ezrin与RhoA两者表达呈显著正相关(Rs=0.486,P<0.001)。
5. Ezrin和RhoA蛋白表达阳性的患者,治疗后1年、3年及5年生存率分别为：75%,55%,33%和84%,60%,33%,均低于阴性表达100%,92%,78%和93%,71%,63%。均有显著性差异(x2=12.943,P=0.000及x2=9.869,P=0.002<0.05)。
结论：
1. Ezrin和RhoA蛋白表达均与NPC的发生可能有关,但更可能是Ezrin和RhoA蛋白表达的NPC细胞本身具有浸润转移潜能。
2. Ezrin和RhoA蛋白表达均参与了NPC的早期局部浸润转移、淋巴结转移和远处器官转移等过程,并很有可能是重要的参与因子。
3. Ezrin与RhoA蛋白表达呈显著正相关,进一步间接证明了两者在结构、功能上和基因表达等方面有着密切联系,同时表明它们很可能为NPC浸润转移的共同或协同促进因子。
4. Ezrin和RhoA与NPC的预后有关。Ezrin或RhoA阳性表达的NPC患者平均生存率低,特别是Ezrin和RhoA同时阳性表达者较Ezrin和RhoA同时阴性表达者生存期短,预后差。
Objective:
To investigate the expression of Ezrin and RhoA proteins in nasopharyngeal carcinoma (NPC) tissue in different clinical stages, and anlyzing their functions and relationships in the NPC carcinogenesis and development mechanism. The purpose were:A. to study their roles in invasion and metastasis of NPC. B. to provide the new theoretical foundation and to produce new valuable indicators for the early diagnosis and the judging prognosis of NPC.
Methods:
1. Specimens paraffin-embedded tissue of 150 NPC with complete clinical data were collected as experiment group, and 20 cases of nasopharyngeal mucosa chronic inflammation paraffin-embedded tissue were chosen to be compare group.
2. Utilize Supervision two-step immunochemical methods to detect expression of Ezrin and RhoA proteins.
3. SPSS(13.0) statistical software was applied for data processing to analysis:A. the correlation between the expression of Ezrin and RhoA proteins and the major clinical pathological characteristics of NPC (Chi-square test and Spearman rank correlation). B. the prognostic relevance between the expression of Ezrin and RhoA proteins and the Post-treatment survival period of NPC, the survival rate was caculated by Kaplan-Meier method and compared by log-rank test.
Results:
1. The positive expression rates of Ezrin and RhoA proteins in NPC tissue were 74.7% and 62.7% and nearly no positive expression in nasopharyngeal mucosa chronic inflammation tissue. There was a statistically significant difference (p<0.001).
2. In TNM stages, the positive expression rates of Ezrin and RhoA proteins in NPC tissue which were 29.4%、65.5%、92.3%、88.5% and 17.6%、52.7%、78.8%、80.8% in T1,T2，T3,T4 stages, There were statistically significant difference between every stages (P<0.05 or P<0.001) besides T3 and T4 stage; 53.8%、71.4%、79.6%、87.9% and 46.2%、54.8%、65.3%、81.8% in No, N1, N2, N3 stages, There were statistically significant differenc between No and N2, No and N3, N1 and N3 (P<0.05); 72.5%、94.7% and 60.3%、84.2% in M0 and M1 stages, There were statistically significant differencebetween two stages (P<0.001)
3. InⅠ、Ⅱ、Ⅲ、Ⅳclinical stages, the positive expression rates of Ezrin and RhoA proteins in NPC tissue were:50%、40%、80.7%、86.9% and 0%、26.7%、64.9%、80.3%, there were statistically significant difference between every stages (P<0.001)
4. The expression of Ezrin and RhoA in NPC were correlated significantly (Rs=0.486, P=0.000)
5. The 1-,3-, and 5-year overall survival (OS) rates of the positive expression of Ezrin and RhoA 75%,55%,33% and 84%,60%,33% lower than which negative expression rates 100%,92%,78% and 93%,71%,63%, there were statistically significant (χ2=12.943, P=0.000 andχ2=9.869, P=0.002).
Conclusions:
1. Ezrin and RhoA protein expression may have relation with the generation of NPC.But the more possibility that is pointing out the positive expression cells maybe have the metastasis potential.
2. Ezin and RhoA protein expression was correlated with TNM stages and clinical stages. It suggested that Ezrin and RhoA were key factors in focal metastasis, lymphatic metastasis, organic metastasis.
3. Ezrin and RhoA protein expression had a significant correlation and made a further proof that, the two proteins in structure, function and genetic expression had a close connection, meanwhile it showed that the two proteins may be synergic facts in the invasion and metastasis of NPC.
4. Ezrin and RhoA were linked with prognosis. The positive expression of Ezrin and RhoA protein in NPC was higher, the survival period will be shorter and prognosis will be worse.. Especially the common positive expression of Ezrin and RhoA protein survival period were obvious shorter than which common negative expression. It will be more significance test Ezrin and RhoA proteins together for predict prognosis.
方法：
1.选取有完整临床资料及随访资料的150例NPC病例石蜡包埋组织标本作为实验组,选取20例鼻咽粘膜慢性炎石蜡包埋组织作为对照。
2.应用免疫组化Supervision二步法分别检测NPC和对照组组织中Ezrin和RhoA蛋白的表达情况。
3.采用SPSS13.0统计软件进行数据处理。用x2检验、Spearman等级相关分析法分析Ezrin和RhoA蛋白表达与NPC患者临床病理特征之间的关系；用Kaplan-Meier法进行单因素生存分析,log-rank法进行样本间生存率曲线差异检验。
结果：
1. Ezrin与RhoA蛋白在NPC组织中的阳性表达率分别为74.7%和62.7%,在对照组组织中基本不表达。两组差异都有非常显著统计学意义(均为P
3. Ezrin与RhoA蛋白阳性表达率在临床分期Ⅰ、Ⅱ、Ⅲ、Ⅳ期中分别为50%、40%、80.7%、86.9%和0%、26.7%、64.9%、80.3%,两指标各期之间均有非常显著统计学意义(均为P<0.001)。
4.NPC组织中Ezrin与RhoA两者表达呈显著正相关(Rs=0.486,P<0.001)。
5. Ezrin和RhoA蛋白表达阳性的患者,治疗后1年、3年及5年生存率分别为：75%,55%,33%和84%,60%,33%,均低于阴性表达100%,92%,78%和93%,71%,63%。均有显著性差异(x2=12.943,P=0.000及x2=9.869,P=0.002<0.05)。
结论：
1. Ezrin和RhoA蛋白表达均与NPC的发生可能有关,但更可能是Ezrin和RhoA蛋白表达的NPC细胞本身具有浸润转移潜能。
2. Ezrin和RhoA蛋白表达均参与了NPC的早期局部浸润转移、淋巴结转移和远处器官转移等过程,并很有可能是重要的参与因子。
3. Ezrin与RhoA蛋白表达呈显著正相关,进一步间接证明了两者在结构、功能上和基因表达等方面有着密切联系,同时表明它们很可能为NPC浸润转移的共同或协同促进因子。
4. Ezrin和RhoA与NPC的预后有关。Ezrin或RhoA阳性表达的NPC患者平均生存率低,特别是Ezrin和RhoA同时阳性表达者较Ezrin和RhoA同时阴性表达者生存期短,预后差。
Objective:
To investigate the expression of Ezrin and RhoA proteins in nasopharyngeal carcinoma (NPC) tissue in different clinical stages, and anlyzing their functions and relationships in the NPC carcinogenesis and development mechanism. The purpose were:A. to study their roles in invasion and metastasis of NPC. B. to provide the new theoretical foundation and to produce new valuable indicators for the early diagnosis and the judging prognosis of NPC.
Methods:
1. Specimens paraffin-embedded tissue of 150 NPC with complete clinical data were collected as experiment group, and 20 cases of nasopharyngeal mucosa chronic inflammation paraffin-embedded tissue were chosen to be compare group.
2. Utilize Supervision two-step immunochemical methods to detect expression of Ezrin and RhoA proteins.
3. SPSS(13.0) statistical software was applied for data processing to analysis:A. the correlation between the expression of Ezrin and RhoA proteins and the major clinical pathological characteristics of NPC (Chi-square test and Spearman rank correlation). B. the prognostic relevance between the expression of Ezrin and RhoA proteins and the Post-treatment survival period of NPC, the survival rate was caculated by Kaplan-Meier method and compared by log-rank test.
Results:
1. The positive expression rates of Ezrin and RhoA proteins in NPC tissue were 74.7% and 62.7% and nearly no positive expression in nasopharyngeal mucosa chronic inflammation tissue. There was a statistically significant difference (p<0.001).
2. In TNM stages, the positive expression rates of Ezrin and RhoA proteins in NPC tissue which were 29.4%、65.5%、92.3%、88.5% and 17.6%、52.7%、78.8%、80.8% in T1,T2，T3,T4 stages, There were statistically significant difference between every stages (P<0.05 or P<0.001) besides T3 and T4 stage; 53.8%、71.4%、79.6%、87.9% and 46.2%、54.8%、65.3%、81.8% in No, N1, N2, N3 stages, There were statistically significant differenc between No and N2, No and N3, N1 and N3 (P<0.05); 72.5%、94.7% and 60.3%、84.2% in M0 and M1 stages, There were statistically significant differencebetween two stages (P<0.001)
3. InⅠ、Ⅱ、Ⅲ、Ⅳclinical stages, the positive expression rates of Ezrin and RhoA proteins in NPC tissue were:50%、40%、80.7%、86.9% and 0%、26.7%、64.9%、80.3%, there were statistically significant difference between every stages (P<0.001)
4. The expression of Ezrin and RhoA in NPC were correlated significantly (Rs=0.486, P=0.000)
5. The 1-,3-, and 5-year overall survival (OS) rates of the positive expression of Ezrin and RhoA 75%,55%,33% and 84%,60%,33% lower than which negative expression rates 100%,92%,78% and 93%,71%,63%, there were statistically significant (χ2=12.943, P=0.000 andχ2=9.869, P=0.002).
Conclusions:
1. Ezrin and RhoA protein expression may have relation with the generation of NPC.But the more possibility that is pointing out the positive expression cells maybe have the metastasis potential.
2. Ezin and RhoA protein expression was correlated with TNM stages and clinical stages. It suggested that Ezrin and RhoA were key factors in focal metastasis, lymphatic metastasis, organic metastasis.
3. Ezrin and RhoA protein expression had a significant correlation and made a further proof that, the two proteins in structure, function and genetic expression had a close connection, meanwhile it showed that the two proteins may be synergic facts in the invasion and metastasis of NPC.
4. Ezrin and RhoA were linked with prognosis. The positive expression of Ezrin and RhoA protein in NPC was higher, the survival period will be shorter and prognosis will be worse.. Especially the common positive expression of Ezrin and RhoA protein survival period were obvious shorter than which common negative expression. It will be more significance test Ezrin and RhoA proteins together for predict prognosis.
引文
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3.尚云峰,田道法.鼻咽癌转移相关分子标志物研究进展,中国中西结合耳鼻咽喉科杂志,2008,16(2),157-160
4.张岩,刘康达.膜-细胞骨架连接分子ezrin在肿瘤生长和转移中的作用,复旦学报(医学版),2007,34(1),153-155
5.王颢,陈玉霞,卢建.Rho家族在肿瘤组织的表达及临床意义,中国癌症杂志,2005,15(4),399-401
6.罗世荣.癌细胞运动与侵袭之间关系的研究进展,国外医学,1989,1,24-28
7. 罗元.细胞迁移运动相关因子与肿瘤浸润转移的关系,中国医学文摘(肿瘤学),2004,18(4),300-301
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2.黄桂彪,黄志碧,姜岳明.鼻咽癌的流行病学特征及其危险因素,工业卫生与职业病,2004,30(4),252-254
3.尚云峰,田道法.鼻咽癌转移相关分子标志物研究进展,中国中西结合耳鼻咽喉科杂志,2008,16(2),157-160
4.张岩,刘康达.膜-细胞骨架连接分子ezrin在肿瘤生长和转移中的作用,复旦学报(医学版),2007,34(1),153-155
5.王颢,陈玉霞,卢建.Rho家族在肿瘤组织的表达及临床意义,中国癌症杂志,2005,15(4),399-401
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