MTDH、HIF-1α和TKTL1在喉癌中的表达及其临床意义

Expression and clinical significance of MTDH,HIF-1α and TKTL1 in laryngeal carcinoma

目的：探究MTDH、HIF-1α、TKTL1在喉鳞状细胞癌中的作用机制及其相互作用。方法：采用免疫组织化学方法检测30例喉鳞状细胞癌组织及20例癌旁正常组织中MTDH、HIF-1α和TKTL1的表达情况,所有实验数据用SPSS 13.0统计软件分析。结果：MTDH、HIF-1α和TKTL1在喉癌组织中的阳性表达率分别为56.67%、60.00%和63.33%,与癌旁组织中阳性表达率20.00%、10.00%和15.00%相比,差异有统计学意义（P〈0.05或P〈0.01）。MTDH、HIF-1α和TKTL1在有淋巴结转移的喉鳞状细胞癌组织中的阳性表达率分别为84.62%、84.62%和79.62%,与无淋巴结转移者中的阳性表达率35.29%、41.18%和35.29%相比,差异有统计学意义（P〈0.05）。MTDH和HIF-1α在病理为中-低分化喉鳞状细胞癌组织中的阳性表达率分别为73.68%和84.21%,与高分化组阳性表达率27.27%和18.18%相比,差异有统计学意义（P〈0.05或P〈0.01）。TKTL1和HIF-1α在Ⅰ~Ⅱ期喉鳞状细胞癌组织中的阳性表达率为25.00%和33.33%,与Ⅲ~Ⅳ期喉鳞状细胞癌组织中阳性表达率72.22%和77.78%相比,差异有统计学意义（P〈0.05）。而3个因子与患者的年龄、吸烟量和肿瘤发生部位无明显相关性（P〉0.05）。Spearman秩相关检测结果显示喉鳞状细胞癌组织中MTDH与HIF-1α表达水平呈正相关（r=0.384,P〈0.05）;TKTL1与HIF-1α表达水平也呈正相关（r=0.508,P〈0.01）;MTDH表达与TKTL1表达无明显相关性（r=-0.107,P〉0.05）。结论：MTDH蛋白、TKTL1蛋白与HIF-1α蛋白相互作用参与喉鳞状细胞癌的发生、浸润和转移;MTDH和TKTL1有望成为喉鳞状细胞癌临床生物治疗的新靶点,并且可为判断喉鳞状细胞癌患者的预后提供理论依据。

Objective：To investigate the functional mechanism of metadherin（MTDH）,hypoxia-inducible factor-1alpha（HIF-1α）and transketolase-like gene 1（TKTL1）and their interaction with each other in laryngeal carcinoma development.Method：Thirty laryngeal carcinoma samples and 20 samples of para-carcinoma tissue were taken from the patients received operation treatment.The expression levels of MTDH,HIF-1αand TKTL1 were detected in all the samples by SP immunohistochemical methods.The data were analyzed by the SPSS13.0 statistical software.Result：The positive expression rate of MTDH,HIF-1α and TKTL1 in the 30 cases of laryngeal carcinoma was 56.67%,60.00% and 63.33%,respectively,which was 20.00%,10.00% and 15.00% respectively in the para-carcinoma tissue,the difference of the positive expression rate of the tested objects between these two groups was statistically significant（P〈0.05 or P〈0.01）.Of the 30 cases of laryngeal carcinoma,the positive expression rate of MTDH,HIF-1αand TKTL1 in the cases with lymphnode metastasis was 84.62%,84.62% and 79.62%,respectively,compared with the rate in those without lymph nodes metastasis,which was 35.29%,41.18% and 35.29%.The difference of the positive expression rate of the tested objects between these two groups was statistically significant（P〈0.05）.In the tissue of poorly differentiated squamons cell carcinoma verified by pathology,the positive expression rates of MTDH and HIF-1α was 73.68% and 84.21%,respectively,while that in the tissue of well differentiated squamous carcinoma was 27.27% and 18.18%.The difference of the positive expression rate of the tested objects between these two groups was statistically significant（P〈0.05 or（P〈0.01）.The positive expression rate of TKTL1 in laryngeal carcinoma at stageⅠ-Ⅱ was 25.00% and that at stageⅢ-Ⅳ was 72.22%,the difference between which was statistically significant（P〈0.05）.The positive expression rate of HIF-1αin laryngeal carcinoma at stage Ⅰ- Ⅱ was 33.33% and that at stage Ⅲ- Ⅳ was 77.78%,the difference between which was statistically significant（P〈0.05）.The expression of MTDH,HIF-1α and TKTL1 showed no relationship with age,smoking amount or the tumor location（P〈0.05）.The Spearman′s rank correlation analysis showed that the positive expression rates of MTDH and HIF-1α in laryngeal carcinoma had positive correlation（r=0.384,P〈0.05）;the positive expression rates of TKTL1 and HIF-1α in laryngeal carcinoma had positive correlation（r=0.508,P〈0.01）;But there was no significant correlation between the positive expression rates of MTDH and TKTL1 in laryngeal carcinoma（r=-0.107,P〈0.05）.Conclusion：It suggested that these three proteins may have close relationship with the occurrence,invasion and metastasis of the laryngeal carcinoma.MTDH and TKTL1 may be expected to be new clinical targets for laryngeal carcinoma treatment and it could offer theoretical basis for the prognosis of the laryngeal carcinoma.