title: Protein tyrosine kinase 6 is associated with nasopharyngeal carcinoma poor prognosis and metastasis.
abstract: BACKGROUND
  The aim of this study was to analyze the expression of protein tyrosine kinase 6 (PTK6) in nasopharyngeal carcinoma (NPC) samples, and to identify whether PTK6 can serve as a biomarker for the diagnosis and prognosis of NPC.
  
  
  METHODS
  We used quantitative RT-PCR and Western blotting analysis to detect mRNA and protein expression of PTK6 in NPC cell lines and immortalized nasopharyngeal epithelial cell lines. 31 NPC and 16 non-tumorous nasopharyngeal mucosa biopsies were collected to detect the difference in the expression of mRNA level of PTK6 by quantitative RT-PCR. We also collected 178 NPC and 10 normal nasopharyngeal epithelial cases with clinical follow-up data to investigate the expression of PTK6 by immunohistochemistry staining (IHC). PTK6 overexpression on cell growth and colony formation ability were measured by the method of cell proliferation assay and colony formation assay.
  
  
  RESULTS
  The expression of PTK6 was higher in most of NPC cell lines at both mRNA and protein levels than in immortalized nasopharyngeal epithelial cell lines (NPECs) induced by Bmi-1 (Bmi-1/NPEC1, and Bmi-1/NPEC2). The mRNA level of PTK6 was high in NPC biopsies compared to non-tumorous nasopharyngeal mucosa biopsies. IHC results showed the expression of PTK6 was significantly correlated to tumor size (P<0.001), clinical stage (P<0.001), and metastasis (P=0.016). The patients with high-expression of PTK6 had a significantly poor prognosis compared to those of low-expression (47.8% versus 80.0%, P<0.001), especially in the patients at the advanced stages (42.2% versus 79.1%, P<0.001). Multivariate analysis indicated that the level of PTK6 expression was an independent prognostic factor for the overall survival of patients with NPC (P <0.001). Overexpression of PTK6 in HNE1 cells enhanced the ability of cell proliferation and colony formation.
  
  
  CONCLUSIONS
  Our results suggest that high-expression of PTK6 is an independent factor for NPC patients and it might serve as a potential prognostic biomarker for patients with NPC.
authors.affiliation: Department of Oncology, Second Affiliated Hospital of Guangzhou medical college, 250 Changgang Road East, Guangzhou 510260, China.
authors.forename: Li-na
authors.initials: LN
authors.lastname: Liu
authors.forename: Pei-yu
authors.initials: PY
authors.lastname: Huang
authors.forename: Zhi-rui
authors.initials: ZR
authors.lastname: Lin
authors.forename: Li-juan
authors.initials: LJ
authors.lastname: Hu
authors.forename: Jian-zhong
authors.initials: JZ
authors.lastname: Liang
authors.forename: Man-zhi
authors.initials: MZ
authors.lastname: Li
authors.forename: Lin-quan
authors.initials: LQ
authors.lastname: Tang
authors.forename: Mu-sheng
authors.initials: MS
authors.lastname: Zeng
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhong
authors.forename: Bo-hang
authors.initials: BH
authors.lastname: Zeng
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; C088375:PTK6 protein, human