Investigation of Clinical Significance and Expression of Tumor Metastasis-related Genes in The Nasopharyngeal Cancer Using Tissue Microarray Technique*

Abstract

To investigate the role of abnormal protein expression of the tumor metastasis related-genes in invasion and metastasis of nasopharyngeal cancer(NPC) and to seek the metastasis-related markers for NPC,high-throughput tissue microarray and immunohistochemistry were used to detect protein expression of membrane type 1-matrix metalloproteinase(MT1-MMP),membrane type 2-matrix metalloproteinase(MT2-MMP),membrane-cytoskeletal crosslinker Ezrin(Ezrin),metastasis suppressor gene nm23-H1,the epithelial cell adhesion molecule E-cadherin(E-cad)and tissue inhibitor of metalloproteinase-2(TIMP-2) in NPC.Results showed that significant high expression of MT1-MMP and Ezrin proteins and very low expression of nm23-H1 and TIMP-2 proteins were found in NPC compared with non-cancerous nasopharyngeal epithelium(P 0.05,P 0.01,respectively).Expression of MT1-MMP,MT2-MMP and Ezrin proteins in the stageⅡ,stageⅢ and Ⅳ NPC and NPC with lymph node metastasis is significantly higher than that of in the stageⅠ NPC and NPC without lymph node metastasis(P0.05,P0.01 respectively),but expression of nm23-H1 protein in the stageⅡ,stageⅢ and Ⅳ NPC and NPC with lymph node metastasis is significantly lower than that of in the stageⅠ NPC and NPC without lymph node metastasis(P 0.05).There were significantly positive correlation between MT1-MMP and MT2-MMP(r = 0.308,P 0.001),nm23-H1 and E-cad(r = 0.167,P 0.05),nm23-H1 and TIMP-2(r = 0.279,P = 0.001);E-cad and TIMP-2(r = 0.279,P = 0.001) in the NPC.Also,there were obviously negative correlation between MT1-MMP and E-cad(r=-0.188,P0.05),MT1-MM and TIMP-2(r=-0.233,P0.05),Ezrin and E-cad(r =-0.204,P 0.05) in NPC.Based on the cluster analysis,there was common higher expression of MT1-MMP,MT2-MMP and Ezrin proteins in the NPC than that of in the chronic inflammatory nasopharyngeal epithelium(P0.05).However,common higher loss expression of nm23-H1,E-cad and TIMP-2 proteins were found in NPC compared with the peri-cancer nasopharyngeal epithelium and chronic inflammatory nasopharyngeal epithelium(P 0.05,P 0.01).Logistic regression analysis and validity estimation indicated that MT1-MMP gene might be better independent prognostic value for metastasis and clinical progress of NPC.The results suggested that high protein expression of multiple metastasis related-genes,low expression of the metastasis suppressor genes and loss balance between metastasis genes and metastasis suppressor genes might play important role in the metastasis and clinical progression of NPC.MT1-MMP protein can be used as the better independent prognostic molecular marker for metastasis of NPC.