ET-1和VEGF-C在喉癌中的表达及临床意义

目的:研究血管内皮素-1(ET-1)和血管内皮生长因子-C(VEGF-C)在喉癌组织中的表达规律,探讨两者与喉癌发生、发展和淋巴结转移的关系及在预后中的意义。方法:选择45例经病理确诊的喉癌组织为实验组,20例喉良性病变组织为对照组,免疫组化法和实时荧光定量PCR法检测ET-1和VEGF-C蛋白和mRNA的表达,5’-核苷酸酶染色法(5’-Nase)计数淋巴管密度(LVD),CD34染色计数微血管密度(MVD),并结合临床病理特征和生存资料进行相关分析。结果:喉癌淋巴结转移组ET-1、VEGF-C蛋白和mRNA表达显著高于未转移组(P<0.05),二者均显著高于良性喉组织(P<0.01)。喉癌组织中ET-1蛋白表达与瘤内和瘤周LVD、MVD、淋巴结转移、淋巴管浸润、TNM临床分期显著相关(P<0.05),与年龄、性别、肿瘤部位及组织学分级无关(P>0.05)。VEGF-C蛋白表达与瘤内和瘤周LVD、淋巴结转移、淋巴管浸润、MVD显著相关(P<0.05),与年龄、性别、肿瘤部位、TNM临床分期及组织学分级无关(P>0.05)。ET-1和VEGF-C在肿瘤组织中的蛋白表达正相关(r=0.456,P=0.001)。生存分析显示ET-1蛋白阳性表达与生存率无关(P>0.05),ET-1+/VEGF-C+、VEGF-C蛋白阳性表达与生存率负相关(P<0.05),其中ET-1+/VEGF-C+阳性表达更具有显著高危死亡率(P=0.000)。Cox回归模型显示ET-1+/VEGF-C+可以独立影响预后(P<0.05)。结论:ET-1和VEGF-C均能促进喉癌淋巴管生成和血管生成。在喉癌组织中ET-1过表达可能通过诱导VEGF-C表达上调促进喉癌淋巴管生成和淋巴结转移。联合检测ET-1及VEGF-C的表达可成为判断喉癌预后的新的生物学指标。

Expressions and their clinical significance of ET-1 and VEGF-C in laryngeal carcinoma

Objective:To investigate the expression of ET-1 and VEGF-C in patients with laryngeal cancer,and their clinical significance and relationship with the development and prognosis of laryngeal carcinoma.Methods: Forty five specimens of laryngeal cancer and twenty benign laryngeal diseases were studied.The expression of ET-1,VEGF-C was observed by immunohistochemistry and real-time fluorescent quantitative PCR.LVD was evaluated by 5′-Nucleotides staining,MVD was evaluated by immunohistochemistry with the specific antibody CD34.The correlation analysis was made between ET-1,VEGF-C and clinical parameters,and judged the role of ET-1,VEGF-C,ET-1+/VEGF-C+ in laryngeal cancer prognosis by using Kaplan-Meier and Cox method.Results:The expressions of ET-1,VEGF-C proteins and mRNA were higher in tumor tissue than in the normal tissue(P<0.01).Compared with no lymphatic metastasis group,the expression of ET-1 and VEGF-C proteins and mRNA were significantly increased in lymphatic metastasis group(P<0.05).The expression of ET-1 was significantly correlated with peritumoral and intratumoral LVD,MVD,TNM stage,lymphatic metastasis and lymphovascular invasion(P<0.05),no significant correlation was found between ET-1 and age,gender,histological stage and location(P>0.05).The expression of VEGF-C was significantly correlated with peritumoral and intratumoral LVD,MVD,lymphatic metastasis and lymphovascular invasion(P<0.05),no significant correlation was found between VEGF-C and age,gender,histological stage,TNM stage and location(P>0.05).If tumors had a high ET-1 expression,a high expression of VEGF-C could also be observed(r=0.373,P<0.01).Kaplan-Meier test indicated the different expression of ET-1 had no effect on survival ratio(P>0.05),but the different expression of ET-1+/VEGF-C+,VEGF-C had effect on survival ratio(P<0.05),As well,ET-1+/VEGF-C+ had significant high risk death rate(P=0.000).Cox model indicated ET-1+/VEGF-C+ could affect survival independently(P<0.05).Conclusion:The expression of ET-1 and VEGF-C was correlated with lymphangiogenesis and angiogenesis.Our results suggest that a lymphangiogenic pathway,in which ET-1 overexpression stimulates vascular endothelial growth factor-C upregulation,probably exists in laryngeal cell carcinoma.Combined detection of the expression of ET-1 and VEGF-C may be helpful for judging prognosis in laryngeal cancer.