title: Identification of nm23-H1 as a metastatic suppressor and prognostic factor in nasopharyngeal carcinoma by proteomic analysis.
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 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).
  
  
  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.
  
  
  CONCLUSIONS
  nm23-H1 behaves as a metastasis suppressor in NPC, and nm23-H1 downregulation in the is a biomarker for poor NPC prognosis.
authors.affiliation: Department of Gerontology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Xuebing
authors.initials: X
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.forename: Jiaquan
authors.initials: J
authors.lastname: Qu
authors.forename: Qiuyan
authors.initials: Q
authors.lastname: He
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Jiaoyang
authors.initials: J
authors.lastname: Li
authors.forename: Xu
authors.initials: X
authors.lastname: Ye
authors.forename: Yali
authors.initials: Y
authors.lastname: Xiang
authors.forename: Hong
authors.initials: H
authors.lastname: Yi
mesh_terms: D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D013058:Mass Spectrometry; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics / Q000378:metabolism*; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D011379:Prognosis; D020543:Proteome / Q000032:analysis / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D054778:NM23 Nucleoside Diphosphate Kinases; D020543:Proteome; D025521:Tumor Suppressor Proteins; C517938:NME1 protein, human