Nuclear localization of Nm23-H1 in head and neck squamous cell carcinoma is associated with radiation resistance

Haeng Ran Park, Se Heon Kim, Sei Young Lee, Ji Min Sung, Ae Ran Park, Suki Kang, Baek Gil Kim, Yoon Pyo Choi, Yong Bae Kim, Nam Hoon Cho

Research output: Contribution to journalArticle

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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. Cancer 2011;117:1864-73.

Original languageEnglish
Pages (from-to)1864-1873
Number of pages10
JournalCancer
Volume117
Issue number9
DOIs
Publication statusPublished - 2011 May 1

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Odds Ratio
Radiation
Cell Line
Oligonucleotide Array Sequence Analysis
Proteomics
Fluorescent Antibody Technique
Western Blotting
Recurrence
Neoplasms
Radiotherapy
Immunohistochemistry
Regression Analysis
Carcinoma, squamous cell of head and neck

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Park, Haeng Ran ; Kim, Se Heon ; Lee, Sei Young ; Sung, Ji Min ; Park, Ae Ran ; Kang, Suki ; Kim, Baek Gil ; Choi, Yoon Pyo ; Kim, Yong Bae ; Cho, Nam Hoon. / Nuclear localization of Nm23-H1 in head and neck squamous cell carcinoma is associated with radiation resistance. In: Cancer. 2011 ; Vol. 117, No. 9. pp. 1864-1873.
@article{ef319ca5658b47ea8ad90bab0cb36ba8,
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. Cancer 2011;117:1864-73.",
author = "Park, {Haeng Ran} and Kim, {Se Heon} and Lee, {Sei Young} and Sung, {Ji Min} and Park, {Ae Ran} and Suki Kang and Kim, {Baek Gil} and Choi, {Yoon Pyo} and Kim, {Yong Bae} and Cho, {Nam Hoon}",
year = "2011",
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Park, HR, Kim, SH, Lee, SY, Sung, JM, Park, AR, Kang, S, Kim, BG, Choi, YP, Kim, YB & Cho, NH 2011, 'Nuclear localization of Nm23-H1 in head and neck squamous cell carcinoma is associated with radiation resistance', Cancer, vol. 117, no. 9, pp. 1864-1873. https://doi.org/10.1002/cncr.25760

Nuclear localization of Nm23-H1 in head and neck squamous cell carcinoma is associated with radiation resistance. / Park, Haeng Ran; Kim, Se Heon; Lee, Sei Young; Sung, Ji Min; Park, Ae Ran; Kang, Suki; Kim, Baek Gil; Choi, Yoon Pyo; Kim, Yong Bae; Cho, Nam Hoon.

In: Cancer, Vol. 117, No. 9, 01.05.2011, p. 1864-1873.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Nuclear localization of Nm23-H1 in head and neck squamous cell carcinoma is associated with radiation resistance

AU - Park, Haeng Ran

AU - Kim, Se Heon

AU - Lee, Sei Young

AU - Sung, Ji Min

AU - Park, Ae Ran

AU - Kang, Suki

AU - Kim, Baek Gil

AU - Choi, Yoon Pyo

AU - Kim, Yong Bae

AU - Cho, Nam Hoon

PY - 2011/5/1

Y1 - 2011/5/1

N2 - 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. Cancer 2011;117:1864-73.

AB - 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. Cancer 2011;117:1864-73.

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