title: Nuclear localization of Nm23-H1 in head and neck squamous cell carcinoma is associated with radiation resistance.
abstract: BACKGROUND
  Although radiation resistance is a primary issue in radiation therapy, attempts to find predictors of radiation resistance have met with little success. The authors therefore aimed to determine predictors for radiation resistance to improve the prognosis of head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  HNSCC cell lines, SCC15, SCC25, and QLL1, irradiated with an acute dose of 4 grays (Gy) (RR-4), a cumulative dose of 60 Gy (RR-60), and a booster dose of 4 Gy over 60 Gy (RR-60 + 4), were used with nonirradiated cell lines. Those were used in cDNA microarray, proteomics, Western blotting, and immunofluorescence, respectively. One hundred five HNSCC tissue samples with radiation resistance were analyzed by immunohistochemistry.
  
  
  RESULTS
  Western blot analysis of RR-60 cell lines was identical to the data of Nm23-H1 overexpression by cDNA array and proteomic screening. Immunofluorescence demonstrated significant nuclear translocation of Nm23-H1 in RR-4 and RR-60 cell lines, and less but still intense nuclear shuttling in RR-60 + 4. Similarly, Nm23-H1 nuclear localization was observed in 20% (21 of 105) of tissue samples. Univariate analysis demonstrated that Nm23-H1 nuclear localization was strongly associated with overall and recurrence-free survival. Multivariate stepwise Cox regression analysis showed that Nm23-H1 nuclear localization (odds ratio [OR], 7.48) and N stage (OR, 2.13) were associated with overall survival, and Nm23-H1 nuclear localization (OR, 3.02), T stage (OR, 1.43), and insufficient tumor margin (OR, 3.27) were associated with recurrence-free survival.
  
  
  CONCLUSIONS
  Overexpression of Nm23-H1, specifically its nuclear translocation, may be a powerful predictor of radiation resistance in HNSCC.
authors.affiliation: Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Se-Heon
authors.initials: SH
authors.lastname: Kim
authors.forename: Sei Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Haeng Ran
authors.initials: HR
authors.lastname: Park
authors.forename: Ji Min
authors.initials: JM
authors.lastname: Sung
authors.forename: Ae Ran
authors.initials: AR
authors.lastname: Park
authors.forename: Suki
authors.initials: S
authors.lastname: Kang
authors.forename: Baek Gil
authors.initials: BG
authors.lastname: Kim
authors.forename: Yoon Pyo
authors.initials: YP
authors.lastname: Choi
authors.forename: Yong-Bae
authors.initials: YB
authors.lastname: Kim
authors.forename: Nam Hoon
authors.initials: NH
authors.lastname: Cho
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics*; D011237:Predictive Value of Tests; D011836:Radiation Tolerance
chemical_list: D014408:Biomarkers, Tumor; D054778:NM23 Nucleoside Diphosphate Kinases