转移相关基因KAI1、Tiam1、XAGE-1b在腺样囊性癌中的表达及意义
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摘要
目的
腺样囊性癌的转移是一个多因素参与、多步骤完成的复杂过程,受许多基因及其产物的调控,包括：肿瘤转移基因、肿瘤转移抑制基因、和其它一些与转移相关的基因。本实验目的在于通过对腺样囊性癌病例的回顾性研究,试图阐明ACC预后与三种转移基因KAI1、Tiam1、XAGE-1b的相关性,为患者的预后和临床靶向治疗提供实验基础。
方法
将临床收集的39例腺样囊性癌标本、12例对照腮腺组织和ACC-2、ACC-M细胞通过组织学染色,观察组织标本和ACC细胞的HE染色、组织标本和ACC细胞免疫组织化学染色(SABC法),抗体为KAI1、Tiam1、XAGE-1b,通过图像采集、图像分析,获得不同研究标本间的光密度值。通过比较和计算不同研究标本间光密度值的差异,分析相互间的相关性。
采用SPSS 13.0软件进行统计分析。统计KAI1、Tiam1、XAGE-1b蛋白表达阳性的MOD值量化指标,用K-S检验各组样本正态性,组间Levene检验检查方差齐性,比较采用t检验,P<0.05为差异有统计学意义。两两间进行pearson相关分析。
结果
检查各组数据,均近似正态分布,Levene检验各组数据方差齐同。
KAIl的表达：在对照腮腺组织中MOD值大于ACC组织标本,P<0.01,提示两者差异有统计学意义；在三次重复实验中ACC-2的MOD值均大于ACC-M,P<0.05,提示两者差异有统计学意义。KAI1蛋白表达与性别、年龄和是否有淋巴结转移无统计学意义,与TNM分期和肿瘤直径有显著关系：TNM分期为Ⅰ～Ⅱ期的KAI1蛋白表达显著高于Ⅲ-Ⅵ期；肿瘤直径≤4cm的KAI1蛋白表达显著高于>4cm的。
Tiam1的表达：在对照腮腺组织中MOD值小于ACC组织标本,P<0.01,提示两者差异有统计学意义；在三次重复实验中ACC-2的MOD值均小于ACC-M,P<0.05,提示两者有差异。Tiam1蛋白表达与性别、年龄和是否有淋巴结转移无统计学意义,与TNM分期和肿瘤直径有显著关系：TNM分期为Ⅲ-Ⅵ期的Tiam1蛋白表达显著高于Ⅰ-Ⅱ期；肿瘤直径>4cm的Tiam1蛋白表达显著高于≤4cm的。
XAGE-lb的表达：在对照腮腺组织中MOD值小于ACC组织标本,P<0.01,提示两者差异有统计学意义；在三次重复实验中ACC-2的MOD值均小于ACC-M,P<0.05,提示两者差异有统计学意义。XAGE-1b蛋白表达与性别、年龄和是否有淋巴结转移无统计学意义,与TNM分期和肿瘤直径有显著关系：TNM分期为Ⅲ-Ⅵ期的XAGE-1b蛋白表达显著高于Ⅰ-Ⅱ期；肿瘤直径>4cm的XAGE-1b蛋白表达显著高于≤4cm的。
KAI1与Tiaml的相关系数r=-0.429,双侧Pearson检验P=0.006(P<0.01),有统计学意义,可见,KAI1与Tiaml高度负相关。Tiaml与XAGE-lb的相关系数r=0.411,双侧Pearson检验P=0.009(P<0.01),有统计学意义,可见Tiam1与XAGE-1b高度正相关。KAI1与XAGE-1的相关系数r=-0.590,双侧Pearson检验P=0.026(P<0.05),有统计学意义,可见KAI1与XAGE-1b负相关。
结论
(1)与对照腮腺组织相比,ACC标本中KAIl低表达、Tiam1和XAGE-1b高表达；
(2)ACC患者临床分期越晚和肿瘤直径越大,KAI1表达越低,Tiaml和XAGE-1b表达越高；KAI1、Tiam1、XAGE-1b表达与性别、年龄和是否有淋巴结转移无统计学意义。
(3)在ACC标本中KAI1与Tiaml高度负相关,Tiam1与XAGE-1b高度正相关,KAI1与XAGE-1b高度负相关。
Objective
Adenoid cystic carcinoma of the transfer is more than one factor involved, many steps to complete the complex process, subject to the regulation of many genes and their products, including:tumor metastasis gene, tumor metastasis suppressor gene, and other genes associated with metastasis. Purpose of this study is adenoid cystic carcinoma patients by retrospective studies to clarify the prognosis of ACC and three kinds of transfer genes KAI1, Tiam1, XAGE-lb relevance for the prognosis and to provide experimental basis for clinical targeted therapy.
Method
39 cases of clinically collected specimens of adenoid cystic carcinoma,12 cases of parotid gland and ACC-2, ACC-M cells by histological staining of tissue and ACC cells in HE staining, tissue and ACC Immunohistochemistry stain (SABC), antibody to KAI1, Tiaml, XAGE-lb, by image acquisition, image analysis, by different research optical density between samples. Calculated by comparing the different studies and samples of the difference between the optical density analysis the correlation between each other.
Using SPSS 13.0 software for statistical analysis. Statistics KAI1, Tiaml, XAGE-lb protein expression in the MOD value of quantitative indicators, with the KS test samples in each group normality, Levene test group check the homogeneity of variance, comparison by t test, P<0.05 as statistically significant difference. Each other to pearson correlation analysis.
Results
Check each set of data, are approximate normal distribution, Levene homogeneity of variance test with each set of data.
KAI1 expression:in the control parotid gland tissue MOD value is greater than the ACC, P<0.01, statistically significant difference between the two tips; in three repeated experiments in the ACC-2 of the MOD values were greater than the ACC-M, P< 0.05, suggesting that the difference was statistically significant. KAI1 protein expression and gender, age, and whether there was no significant lymph node metastasis, and TNM staging and tumor size was significantly related:TNM stage wasⅠ-Ⅱof the KAI1 protein was significantly higher than that ofⅢ-Ⅵ; tumor diameter≤4cm of KAI1 protein was significantly higher than those> 4cm's.
Tiaml expression:in the control parotid gland tissue MOD value is less than ACC, P<0.01, statistically significant difference between the two tips; in three repeated experiments in the ACC-2 of the MOD values were less than ACC-M, P< 0.05, suggesting that there are differences. Tiaml protein expression and gender, age, and whether there was no significant lymph node metastasis, and TNM staging and tumor size was significantly related:TNM stage wasⅢ-Ⅵof the Tiaml protein was significantly higher than theⅠ-Ⅱperiod; tumor diameter> 4cm of Tiaml protein expression was significantly higher than the≤4cm's.
XAGE-lb expression:in the control parotid gland tissue MOD value is less than ACC, P<0.01, statistically significant difference between the two tips; in three repeated experiments in the ACC-2 of the MOD values were less than ACC-M, P<0.05, statistically significant difference between the two tips. XAGE-lb protein expression and gender, age, and whether there was no significant lymph node metastasis, and TNM staging and tumor size was significantly related:TNM stage wasⅢ-Ⅵof the XAGE-1b protein was significantly higher than theⅠ-Ⅱperiod; tumor size> 4cm in XAGE-1b protein was significantly higher than the≤4cm's.
The correlation coefficient of KAI1 and Tiaml r=-0.429, bilateral Pearson test P =0.006 (P<0.01), statistically significant, visible, KAI1 a high negative correlation with Tiaml. Tiaml and XAGE-lb of the correlation coefficient r=0.411, bilateral Pearson test P= 0.009 (P<0.01), statistically significant, Tiaml and XAGE-lb shows a high degree of correlation. KAI1 and XAGE-1 correlation coefficient r=-0.590, bilateral Pearson test P=0.026 (P<0.05), statistically significant, KAI1 and XAGE-lb shows negative correlation.
Conclusions
(1), parotid gland, compared with the control, ACC samples, low expression of KAI1, Tiaml and XAGE-1b overexpression.
(2) ACC clinical stage in patients with the later and larger tumor size, KAI1 expression in the lower, Tiaml and XAGE-1b higher expression; KAI1, Tiam1, XAGE-1b expression and gender, age, and whether there is lymph node metastasis and significance.
(3) KAI1 in the ACC samples were highly correlated with Tiaml, Tiam1 XAGE-1b with a high positive correlation, KAI1 and XAGE-1b high negative correlation.
腺样囊性癌的转移是一个多因素参与、多步骤完成的复杂过程,受许多基因及其产物的调控,包括：肿瘤转移基因、肿瘤转移抑制基因、和其它一些与转移相关的基因。本实验目的在于通过对腺样囊性癌病例的回顾性研究,试图阐明ACC预后与三种转移基因KAI1、Tiam1、XAGE-1b的相关性,为患者的预后和临床靶向治疗提供实验基础。
方法
将临床收集的39例腺样囊性癌标本、12例对照腮腺组织和ACC-2、ACC-M细胞通过组织学染色,观察组织标本和ACC细胞的HE染色、组织标本和ACC细胞免疫组织化学染色(SABC法),抗体为KAI1、Tiam1、XAGE-1b,通过图像采集、图像分析,获得不同研究标本间的光密度值。通过比较和计算不同研究标本间光密度值的差异,分析相互间的相关性。
采用SPSS 13.0软件进行统计分析。统计KAI1、Tiam1、XAGE-1b蛋白表达阳性的MOD值量化指标,用K-S检验各组样本正态性,组间Levene检验检查方差齐性,比较采用t检验,P<0.05为差异有统计学意义。两两间进行pearson相关分析。
结果
检查各组数据,均近似正态分布,Levene检验各组数据方差齐同。
KAIl的表达：在对照腮腺组织中MOD值大于ACC组织标本,P<0.01,提示两者差异有统计学意义；在三次重复实验中ACC-2的MOD值均大于ACC-M,P<0.05,提示两者差异有统计学意义。KAI1蛋白表达与性别、年龄和是否有淋巴结转移无统计学意义,与TNM分期和肿瘤直径有显著关系：TNM分期为Ⅰ～Ⅱ期的KAI1蛋白表达显著高于Ⅲ-Ⅵ期；肿瘤直径≤4cm的KAI1蛋白表达显著高于>4cm的。
Tiam1的表达：在对照腮腺组织中MOD值小于ACC组织标本,P<0.01,提示两者差异有统计学意义；在三次重复实验中ACC-2的MOD值均小于ACC-M,P<0.05,提示两者有差异。Tiam1蛋白表达与性别、年龄和是否有淋巴结转移无统计学意义,与TNM分期和肿瘤直径有显著关系：TNM分期为Ⅲ-Ⅵ期的Tiam1蛋白表达显著高于Ⅰ-Ⅱ期；肿瘤直径>4cm的Tiam1蛋白表达显著高于≤4cm的。
XAGE-lb的表达：在对照腮腺组织中MOD值小于ACC组织标本,P<0.01,提示两者差异有统计学意义；在三次重复实验中ACC-2的MOD值均小于ACC-M,P<0.05,提示两者差异有统计学意义。XAGE-1b蛋白表达与性别、年龄和是否有淋巴结转移无统计学意义,与TNM分期和肿瘤直径有显著关系：TNM分期为Ⅲ-Ⅵ期的XAGE-1b蛋白表达显著高于Ⅰ-Ⅱ期；肿瘤直径>4cm的XAGE-1b蛋白表达显著高于≤4cm的。
KAI1与Tiaml的相关系数r=-0.429,双侧Pearson检验P=0.006(P<0.01),有统计学意义,可见,KAI1与Tiaml高度负相关。Tiaml与XAGE-lb的相关系数r=0.411,双侧Pearson检验P=0.009(P<0.01),有统计学意义,可见Tiam1与XAGE-1b高度正相关。KAI1与XAGE-1的相关系数r=-0.590,双侧Pearson检验P=0.026(P<0.05),有统计学意义,可见KAI1与XAGE-1b负相关。
结论
(1)与对照腮腺组织相比,ACC标本中KAIl低表达、Tiam1和XAGE-1b高表达；
(2)ACC患者临床分期越晚和肿瘤直径越大,KAI1表达越低,Tiaml和XAGE-1b表达越高；KAI1、Tiam1、XAGE-1b表达与性别、年龄和是否有淋巴结转移无统计学意义。
(3)在ACC标本中KAI1与Tiaml高度负相关,Tiam1与XAGE-1b高度正相关,KAI1与XAGE-1b高度负相关。
Objective
Adenoid cystic carcinoma of the transfer is more than one factor involved, many steps to complete the complex process, subject to the regulation of many genes and their products, including:tumor metastasis gene, tumor metastasis suppressor gene, and other genes associated with metastasis. Purpose of this study is adenoid cystic carcinoma patients by retrospective studies to clarify the prognosis of ACC and three kinds of transfer genes KAI1, Tiam1, XAGE-lb relevance for the prognosis and to provide experimental basis for clinical targeted therapy.
Method
39 cases of clinically collected specimens of adenoid cystic carcinoma,12 cases of parotid gland and ACC-2, ACC-M cells by histological staining of tissue and ACC cells in HE staining, tissue and ACC Immunohistochemistry stain (SABC), antibody to KAI1, Tiaml, XAGE-lb, by image acquisition, image analysis, by different research optical density between samples. Calculated by comparing the different studies and samples of the difference between the optical density analysis the correlation between each other.
Using SPSS 13.0 software for statistical analysis. Statistics KAI1, Tiaml, XAGE-lb protein expression in the MOD value of quantitative indicators, with the KS test samples in each group normality, Levene test group check the homogeneity of variance, comparison by t test, P<0.05 as statistically significant difference. Each other to pearson correlation analysis.
Results
Check each set of data, are approximate normal distribution, Levene homogeneity of variance test with each set of data.
KAI1 expression:in the control parotid gland tissue MOD value is greater than the ACC, P<0.01, statistically significant difference between the two tips; in three repeated experiments in the ACC-2 of the MOD values were greater than the ACC-M, P< 0.05, suggesting that the difference was statistically significant. KAI1 protein expression and gender, age, and whether there was no significant lymph node metastasis, and TNM staging and tumor size was significantly related:TNM stage wasⅠ-Ⅱof the KAI1 protein was significantly higher than that ofⅢ-Ⅵ; tumor diameter≤4cm of KAI1 protein was significantly higher than those> 4cm's.
Tiaml expression:in the control parotid gland tissue MOD value is less than ACC, P<0.01, statistically significant difference between the two tips; in three repeated experiments in the ACC-2 of the MOD values were less than ACC-M, P< 0.05, suggesting that there are differences. Tiaml protein expression and gender, age, and whether there was no significant lymph node metastasis, and TNM staging and tumor size was significantly related:TNM stage wasⅢ-Ⅵof the Tiaml protein was significantly higher than theⅠ-Ⅱperiod; tumor diameter> 4cm of Tiaml protein expression was significantly higher than the≤4cm's.
XAGE-lb expression:in the control parotid gland tissue MOD value is less than ACC, P<0.01, statistically significant difference between the two tips; in three repeated experiments in the ACC-2 of the MOD values were less than ACC-M, P<0.05, statistically significant difference between the two tips. XAGE-lb protein expression and gender, age, and whether there was no significant lymph node metastasis, and TNM staging and tumor size was significantly related:TNM stage wasⅢ-Ⅵof the XAGE-1b protein was significantly higher than theⅠ-Ⅱperiod; tumor size> 4cm in XAGE-1b protein was significantly higher than the≤4cm's.
The correlation coefficient of KAI1 and Tiaml r=-0.429, bilateral Pearson test P =0.006 (P<0.01), statistically significant, visible, KAI1 a high negative correlation with Tiaml. Tiaml and XAGE-lb of the correlation coefficient r=0.411, bilateral Pearson test P= 0.009 (P<0.01), statistically significant, Tiaml and XAGE-lb shows a high degree of correlation. KAI1 and XAGE-1 correlation coefficient r=-0.590, bilateral Pearson test P=0.026 (P<0.05), statistically significant, KAI1 and XAGE-lb shows negative correlation.
Conclusions
(1), parotid gland, compared with the control, ACC samples, low expression of KAI1, Tiaml and XAGE-1b overexpression.
(2) ACC clinical stage in patients with the later and larger tumor size, KAI1 expression in the lower, Tiaml and XAGE-1b higher expression; KAI1, Tiam1, XAGE-1b expression and gender, age, and whether there is lymph node metastasis and significance.
(3) KAI1 in the ACC samples were highly correlated with Tiaml, Tiam1 XAGE-1b with a high positive correlation, KAI1 and XAGE-1b high negative correlation.
引文
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