Identification of nm23-H1 as a metastatic suppressor and prognostic factor in nasopharyngeal carcinoma by proteomic analysis / 中南大学学报(医学版)

ABSTRACT

Objective:To identify proteins associated with nasopharyngeal carcinoma (NPC) metastasis,and provide scientific basis for the prevention and cure of NPC.Methods: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 used siRNA 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).Results: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.Conclusion:nm23-H1 behaves as a metastasis suppressor in NPC,and nm23-H1 downregulation is a biomarker for poor NPC prognosis.