臺灣博碩士論文加值系統

口腔鱗狀上皮細胞癌在台灣十分常見，且大部分有高復發風險的病人在術後還需要接受放射線治療或是化學治療。Rad51是一種已知的DNA修補蛋白，它在homologous recombination的過程中扮演著重要的角色。Rad51蛋白的過度表現已在很多不同的癌症上被發現且一般被視為一個不好的預後指標。因此，此研究的目的主要是探討Rad51蛋白在口腔癌症患者上的表現及其所扮演的角色。

Oral squamous cell carcinoma (OSCC) is very common in Taiwan and most patients with high adverse factors will receive adjuvant radiotherapy or chemotherapy after surgery. Rad51 is a well known DNA repair protein and serves a central role in homologous recombination. Rad51 overexpression has been reported in several different types of cancer and served as an inferior prognostic marker. Therefore, the aim of the study is to determine the role of Rad51 in oral cancer.

Contents
中文摘要..1
English Abstract ..3
致謝..5
Introduction..6
Literature Review..7
1. Overview of oral squamous cell carcinoma (OSCC)..7
2. Overview of DNA DSBs repair..8
3. Rad51 and cancer..9
Materials and Methods..10
1. Patient samples ..10
2. Tissue microarray..10
3. Immunohistochemistry ..10
4. Assessment of Rad51 staining in oral cancer..12
5. Statistical analysis..12
Results..14
1. Patients’ baseline characteristics ..14
2. Pattern of Rad51 expression in OSCC and correlation to clinical and pathological parameters ..14
3. Relationship between overall survival and Rad51 expression ..15
4. Relationship between PFS and Rad51 expression ..16
5. The relationship between Rad51 and treatment response after radiotherapy and chemotherapy ..17
Discussion ..18
1. Correlation between Rad51 expression and clinicopathological factors..18
2. Rad51 expression and survival in OSCC ..19
3. Rad51 expression and treatment resistance to chemotherapy and radiotherapy in OSCC..20
4. Limitation..20
Conclusion ..22
References..23
Appendix..27

1. Montero, P.H. and S.G. Patel, Cancer of the oral cavity. Surg Oncol Clin N Am, 2015. 24(3): p. 491-508.
2. Baumann P, W.S.C., Role of the human RAD51 protein in homologous recombination and double-stranded-break repair. Trends Biochemi Sci. , 1998. 23(7): p. 247-51.
3. Hu, J., N. Wang, and Y.J. Wang, XRCC3 and RAD51 expression are associated with clinical factors in breast cancer. PLoS One, 2013. 8(8): p. e72104.
4. Qiao, G.B., et al., High-level expression of Rad51 is an independent prognostic marker of survival in non-small-cell lung cancer patients. Br J Cancer, 2005. 93(1): p. 137-43. 5. Nakanoko, T., et al., Rad51 expression is a useful predictive factor for the efficacy of neoadjuvant chemoradiotherapy in squamous cell carcinoma of the esophagus. Ann Surg Oncol, 2014. 21(2): p. 597-604.
6. Li, Y., et al., Elevated expression of Rad51 is correlated with decreased survival in resectable esophageal squamous cell carcinoma. J Surg Oncol, 2011. 104(6): p. 617-22.
7. Health Promotion Administration MoHaW: Taiwan Cancer Registry report, 2013 edition. Health Promotion Administration, Ministry of Health and Welfare, 2016.
8. Chiang, C.J., et al., Incidence and survival of adult cancer patients in Taiwan, 2002-2012. J Formos Med Assoc, 2016.
9. Ko YC, H.Y., Lee CH, Chen MJ, Litt LM, Tsai CC, Betel quid chewing, cigarette smoking and alcohol consumption related to oral cancer in Taiwan. J Oral Pathol Med, 1995. 24(10): p. 450-3.
10. Liu, S.Y., et al., Surgical outcomes and prognostic factors of oral cancer associated with betel quid chewing and tobacco smoking in Taiwan. Oral Oncol, 2010. 46(4): p. 276-82.
11. Huang, C.C., et al., Life expectancy and expected years of life lost to oral cancer in Taiwan: a nation-wide analysis of 22,024 cases followed for 10 years. Oral Oncol, 2015. 51(4): p. 349-54.
12. Hosoya, N. and K. Miyagawa, Targeting DNA damage response in cancer therapy. Cancer Sci, 2014. 105(4): p. 370-88.
13. Richardson, C., RAD51, genomic stability, and tumorigenesis. Cancer Lett, 2005. 218(2): p. 127-39.
14. Mitra, A., et al., Overexpression of RAD51 occurs in aggressive prostatic cancer. Histopathology, 2009. 55(6): p. 696-704.
15. Klein, H.L., The consequences of Rad51 overexpression for normal and tumor cells. DNA Repair (Amst), 2008. 7(5): p. 686-93.
16. Raderschall, E., et al., Elevated levels of Rad51 recombination protein in tumor cells. Cancer Res, 2002. 62(1): p. 219-25.
17. Hansen, L.T., et al., The role of RAD51 in etoposide (VP16) resistance in small cell lung cancer. Int J Cancer, 2003. 105(4): p. 472-9.
18. Vispe, S., et al., Overexpression of Rad51 protein stimulates homologous recombination and increases resistance of mammalian cells to ionizing radiation. Nucleic Acids Res, 1998. 26(12): p. 2859-64.
19. Connell, P.P., et al., Pilot study examining tumor expression of RAD51 and clinical outcomes in human head cancers. Int J Oncol, 2006. 28(5): p. 1113-9.
20. Remmele, W. and H.E. Stegner, Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe, 1987. 8(3): p. 138-40.
21. Kotova, N., et al., Genotoxicity of alcohol is linked to DNA replication-associated damage and homologous recombination repair. Carcinogenesis, 2013. 34(2): p. 325-