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DNA Ligase4 as a Prognostic Marker in Nasopharyngeal Cancer Patients Treated with Radiotherapy

  • Kim, Dong Hyun (Department of Internal Medicine, Dong-A University College of Medicine) ;
  • Oh, Sung Yong (Department of Internal Medicine, Dong-A University College of Medicine) ;
  • Kim, So Yeon (Department of Internal Medicine, Dong-A University College of Medicine) ;
  • Lee, Seul (Department of Internal Medicine, Dong-A University College of Medicine) ;
  • Koh, Myeong Seok (Department of Internal Medicine, Dong-A University College of Medicine) ;
  • Lee, Ji Hyun (Department of Internal Medicine, Dong-A University College of Medicine) ;
  • Lee, Suee (Department of Internal Medicine, Dong-A University College of Medicine) ;
  • Kim, Sung-Hyun (Department of Internal Medicine, Dong-A University College of Medicine) ;
  • Park, Heon Soo (Department of Otolaryngology-Head and Neck Surgery, Dong-A University College of Medicine) ;
  • Hur, Won Joo (Department of Radiation Oncology, Dong-A University College of Medicine) ;
  • Jeong, Jin Sook (Department of Pathology, Dong-A University College of Medicine) ;
  • Ju, Mi Ha (Department of Pathology, Dong-A University College of Medicine) ;
  • Seol, Young Mi (Internal Medicine, Pusan National University Hospital, College of Medicine) ;
  • Choi, Young-Jin (Internal Medicine, Pusan National University Hospital, College of Medicine) ;
  • Chung, Joo Seop (Internal Medicine, Pusan National University Hospital, College of Medicine) ;
  • Kim, Hyo-Jin (Department of Internal Medicine, Dong-A University College of Medicine)
  • Published : 2015.01.22

Abstract

Background: The capability for DNA double-strand breaks (DSBs) repair is crucial for inherent radiosensitivity of tumor and normal cells. We have investigated the clinicopathologic significance of DNA repair gene expression in nasopharyngeal (NP) carcinoma. Materials and Methods: A total of 65 NP cancer patients who received radiotherapy were included. The immunopositivity to Ku 70, DNA-PKcs, MRN, RAD50, XRCC4, and LIG4 were examined in all tumor tissues. Results: The patients comprised 42 males and 23 females, with a median age of 56 years (range, 18-84). The expression levels of RAD50 (0,+1,+2,+3) were 27.7%, 32.3%, 21.5%, and 18.5%. LIG4 (${\pm}$) were 43.1% and 56.9% respectively. The 5-year OS rate of patients with LIG4 (${\pm}$) were 90% and 67.9%, respectively (p=0.035). The 5-year TTP rate of patients with LIG4 (${\pm}$) were 75.9%, 55.5%, respectively (P=0.039). Conclusions: Our results suggest the possibility of predicting the radiosensitivity of NP cancer by performing immunohistochemical analysis of LIG4.

Acknowledgement

Supported by : Dong-A University

References

  1. Ehlers JP, Harbour JW (2005). NBS1 expression as a prognostic marker in uveal melanoma. Clin Cancer Res, 11, 1849-53. https://doi.org/10.1158/1078-0432.CCR-04-2054
  2. Ferlay J, Shin HR, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-917. https://doi.org/10.1002/ijc.25516
  3. Hoeijmakers JH (2009). DNA damage, aging, and cancer. N Engl J Med, 361, 1475-85. https://doi.org/10.1056/NEJMra0804615
  4. Iliakis G (2009). Backup pathways of NHEJ in cells of higher eukaryotes: cell cycle dependence. Radiother Oncol, 92, 310-5. https://doi.org/10.1016/j.radonc.2009.06.024
  5. Kim YJ, Go H, Wu HG, et al (2011). Immunohistochemical study identifying prognostic biomolecular markers in nasopharyngeal carcinoma treated by radiotherapy. Head Neck, 33, 1458-66. https://doi.org/10.1002/hed.21611
  6. Komuro Y, Watanabe T, Hosoi Y, et al (2002). The expression pattern of Ku correlates with tumor radiosensitivity and disease free survival in patients with rectal carcinoma. Cancer, 95, 1199-205. https://doi.org/10.1002/cncr.10807
  7. Kwong DL, Sham JS, Au GK, et al (2004). Concurrent and adjuvant chemotherapy for nasopharyngeal carcinoma: a factorial study. J Clin Oncol, 22, 2643-53. https://doi.org/10.1200/JCO.2004.05.173
  8. Lee SW, Cho KJ, Park JH, et al (2005). Expressions of Ku70 and DNA-PKcs as prognostic indicators of local control in nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys, 62, 1451-7. https://doi.org/10.1016/j.ijrobp.2004.12.049
  9. Ma BB, Hui EP, Chan AT (2008). Systemic approach to improving treatment outcome in nasopharyngeal carcinoma: current and future directions. Cancer Sci, 99, 1311-8. https://doi.org/10.1111/j.1349-7006.2008.00836.x
  10. Parkin DM, Bray F, Ferlay J, et al (2005). Global cancer statistics, 2002. CA Cancer J Clin, 55, 74-108. https://doi.org/10.3322/canjclin.55.2.74
  11. Pavon MA, Parreno M, Leon X, et al (2008). Ku70 predicts response and primary tumor recurrence after therapy in locally advanced head and neck cancer. Int J Cancer, 123, 1068-79. https://doi.org/10.1002/ijc.23635
  12. Sakata K, Matsumoto Y, Tauchi H, et al (2001). Expression of genes involved in repair of DNA double-strand breaks in normal and tumor tissues. Int J Radiat Oncol Biol Phys, 49, 161-7. https://doi.org/10.1016/S0360-3016(00)01352-3
  13. Soderlund K, Stal O, Skoog L, et al (2007). Intact Mre11/Rad50/Nbs1 complex predicts good response to radiotherapy in early breast cancer. Int J Radiat Oncol Biol Phys, 68, 50-8. https://doi.org/10.1016/j.ijrobp.2006.12.005
  14. Stephen BE DR, Carolyn CC, April GF, et al (2010). AJCC cancer staging manual. 7th ed. Philadelphia. edn.
  15. Teo P, Yu P, Lee WY, et al (1996). Significant prognosticators after primary radiotherapy in 903 nondisseminated nasopharyngeal carcinoma evaluated by computer tomography. Int J Radiat Oncol Biol Phys, 36, 291-304.
  16. Davis AJ, Chen DJ (2013). DNA double strand break repair via non-homologous end-joining. Transl Cancer Res, 2, 130-43.
  17. Dikomey E, Dahm-Daphi J, Brammer I, et al (1998). Correlation between cellular radiosensitivity and non-repaired double-strand breaks studied in nine mammalian cell lines. Int J Radiat Biol, 73, 269-78. https://doi.org/10.1080/095530098142365
  18. Bouchaert P, Guerif S, Debiais C, et al (2012). DNA-PKcs expression predicts response to radiotherapy in prostate cancer. Int J Radiat Oncol Biol Phys, 84, 1179-85. https://doi.org/10.1016/j.ijrobp.2012.02.014
  19. Chang ET, Adami HO (2006). The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev, 15, 1765-77. https://doi.org/10.1158/1055-9965.EPI-06-0353
  20. Chua DT, Nicholls JM, Sham JS, et al (2004). Prognostic value of epidermal growth factor receptor expression in patients with advanced stage nasopharyngeal carcinoma treated with induction chemotherapy and radiotherapy. Int J Radiat Oncol Biol Phys, 59, 11-20. https://doi.org/10.1016/j.ijrobp.2003.10.038
  21. Chua DT, Sham JS, Au GK, et al (2002). Concomitant chemoirradiation for stage III-IV nasopharyngeal carcinoma in Chinese patients: results of a matched cohort analysis. Int J Radiat Oncol Biol Phys, 53, 334-43. https://doi.org/10.1016/S0360-3016(02)02710-4
  22. Wilson CR, Davidson SE, Margison GP, et al (2000). Expression of Ku70 correlates with survival in carcinoma of the cervix. Br J Cancer, 83, 1702-6. https://doi.org/10.1054/bjoc.2000.1510
  23. Yang MH, Chiang WC, Chou TY, et al (2006). Increased NBS1 expression is a marker of aggressive head and neck cancer and overexpression of NBS1 contributes to transformation. Clin Cancer Res, 12, 507-15. https://doi.org/10.1158/1078-0432.CCR-05-1231
  24. Zhao HJ, Hosoi Y, Miyachi H, et al (2000). DNA-dependent protein kinase activity correlates with Ku70 expression and radiation sensitivity in esophageal cancer cell lines. Clin Cancer Res, 6, 1073-8.

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