Identification of nm23-H1 as a metastatic suppressor and prognostic factor in nasopharyngeal carcinoma by proteomic analysis.

Abstract

To identify proteins associated with nasopharyngeal carcinoma (NPC) metastasis, and provide scientific basis for the prevention and cure of NPC. A two-dimensional gel electrophoresis and mass spectrometry were performed to screen for differential proteins between highly metastatic 5-8F and non-metastatic 6-10B NPC cell lines. Western blot was used to confirm the differential proteins. We siRNA used to inhibit the expression of differential protein nm23-H1 to determine the association of nm23-H1 with NPC in vitro invasive ability. Immunohistochemistry and statistics were used to evaluate the correlation of nm23-H1 expression with clinicopathological features and clinical outcomes in paraffin-embedded archival tissues including 93 cases of primary NPC and 20 cases of cervical lymphonode metastatic NPC (LMNPC). A total of 15 differential proteins in the 2 cell lines were identified by a proteomic approach, and 3 differential proteins were selectively confirmed. Downregulation of nm23-H1 by siRNA significantly increased the in vitro invasive ability of 6-10B. Significant nm23-H1 downregulation was observed in LMNPC compared with primary NPC. nm23-H1 downregulation in primary NPC was positively correlated with lymphonode and distant metastasis, advanced clinical stage and recurrence. Survival curves showed that patients with nm23-H1 downregulation in primary NPC had a poor prognosis. Multivariate analysis confirmed that nm23-H1 expression level in primary NPC was an independent prognostic indicator. nm23-H1 behaves as a metastasis suppressor in NPC, and nm23-H1 downregulation in the is a biomarker for poor NPC prognosis.