title: Quantitative proteome analysis of overexpressed Cripto-1 tumor cell reveals 14-3-3γ as a novel biomarker in nasopharyngeal carcinoma.
abstract: We previously found that Cripto-1 is involved in the tumorigenesis of nasopharyngeal carcinoma (NPC). Here, to identify new NPC related proteins and to investigate the clinicopathological correlations of it in NPC, Cripto-1 over-expressed cell (CNE1/CR1(+)) was established. Two-dimensional difference in gel electrophoresis (2D-DIGE) analysis and matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS) were used to identify 23 differential proteins in CNE1/CR1(+) and parental cells. Among them, 14-3-3γ showed the potential to be a NPC related protein. 14-3-3γ expression was found in 58.3% (60/103) tumor tissues as detected by IHC, and 69.6% (16/23) NPC fresh tumors expressed higher 14-3-3γ than paired non-cancerous tissues as detected by Western blot. Moreover, 14-3-3γ expression was positively correlated with N classification (p=0.031), distant metastasis (M classification, p=0.018) and clinical stage (p=0.046) of NPC patients. As determined by the Kaplan-Meier method, 14-3-3γ expression in NPC was significantly associated with overall survival (p=0.015). Multivariate analysis also showed that the expression of 14-3-3γ protein was an independent prognostic factor for outcome of NPC. In this study, we identified upregulated 14-3-3γ by 2D-DIGE in CNE1/CR-1(+). We also demonstrated that 14-3-3γ might be a potential biomarker for the prognosis of patients with NPC.
  
  
  CONCLUSIONS
  We believe that three aspects of this manuscript will make it interesting to general readers of Journal of Proteomics. Firstly, based on our previous report, we further validated that Cripto-1 can promote the proliferation and invasion of nasopharyngeal carcinoma (NPC). In this context, we used 2D-DIGE to identify new NPC related proteins. As a result, 14-3-3γ showed the potential to be a candidate. Secondly, we reported for the first time that the expression level of 14-3-3γ was significantly increased in human NPC patient tissues, and 14-3-3γ overexpression correlated statistically with N classification, distant metastasis, and clinical stage. Our results highlight the clinical significance of 14-3-3γ in NPC. Finally, we found that high 14-3-3γ expression is associated with poor survival in NPC patients. Thus, this study has identified that the 14-3-3γ involves in the carcinogenesis of NPC. Our findings may also provide new insights into understanding the molecular mechanism involved in NPC carcinogenesis and progression, and may lead to the development of new approaches for effective diagnosis and therapy.
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China. wuzhengrong@gmail.com
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Wu
authors.forename: Desheng
authors.initials: D
authors.lastname: Weng
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D048948:14-3-3 Proteins / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D020543:Proteome / Q000096:biosynthesis*; D040901:Proteomics / Q000379:methods; D015996:Survival Rate
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D020543:Proteome