上皮性卵巢癌是婦科癌症中最致命的疾病。雖然近年來已有在手術及化學治療藥物的進步，上皮性卵巢癌的治療失敗率仍是很高。針對其高死亡率的其中一項原因，即是對於上皮性卵巢癌形成的分子機轉仍不是十分清楚。為了改善病人臨床治療的成功率，尋求上皮性卵巢癌致病的相關基因是刻不容緩的事。Castor是一個zinc finger轉錄因子，會控制神經元細胞之生長與死亡。最近人類Castor基因(CASZ1)被找到，同時也發現Castor基因(CASZ1)會表現在一些人類的腫瘤中。在神經母細胞瘤中，研究發現喪失CASZ1的表現會有病人較差的預後，同時重建CASZ1的功能可以抑制神經母細胞瘤的腫瘤成長。因此認為CASZ1為抑癌基因。但是分析由成大醫院自行建立的上皮性卵巢癌病人microarray data中，我們發現CASZ1的表現反而較高，同時由國外其他卵巢癌病人data set中，也發現CASZ1的表現高之病人，有較差的臨床預後。這些結果都與在神經母細胞瘤的研究相反。由於此基因在卵巢癌的功能及角色都尚不明，本研究將進一步確定CASZ1基因在上皮性卵巢癌組織的高度表現及與上皮性卵巢癌病人預後關係，並且研究CASZ1與上皮性卵巢癌細胞惡性度的功能相關性，還有在動物實驗中證實CASZ1基因在上皮性卵巢癌所扮演的功能。
從實驗結果可以發現CASZ1在上皮性卵巢癌細胞中的異常表現，反而會促進細胞生長、移行及侵襲的能力並且可能影響上皮性卵巢癌的進展，而從動物實驗也發現抑制CASZ1的表現明顯降低上皮性卵巢癌細胞的生長，另外，我們使用免疫組織化學染色在上皮性卵巢癌病患之組織檢體，透過Kaplan-Meier survival的分析，我們也發現CASZ1和CA125表現量較高的上皮性卵巢癌病患會有較差的overall srvival (OS) 和Progression-free survival(PFS)，可能有助於上皮性卵巢癌病患的預後不良。所以，CASZ1的表現量，在臨床上或許可用於鑑定上皮性卵巢癌病患患者更積極的輔助治療。
在完成本計畫後，可以使我們對於CASZ1基因在上皮性卵巢癌的功能更加了解，也期待將來可以利用這些成果增加上皮性卵巢癌病人的治療成功率且希望能釐清此基因在上皮性卵巢癌的角色。

Epithelial ovarian cancer is the most lethal gynecological malignancy. Despite of the improvement of surgical techniques and chemotherapy regimens, the patient outcome is still not good. Ovarian cancers are counted for the high mortality rate due to the unclear mechanism of molecular pathogenesis. To improve the patients’ clinical outcome, it is desirable to identify of the genes associated with epithelial ovarian cancer. Castor is a zinc finger transcription factor that controls the growth and death of neuroblastoma cell in Drosophila melanogaster. Recently, a human castor gene (CASZ1) was cloned and it is structurally homologous to Drosophila castor. CASZ1 is expressed in a number of human tumors. In neuroblastoma tumors, loss of CASZ1 is associated with poor prognosis and restoration of CASZ1 function suppresses neuroblastoma tumorigenicity. However, based on the microarray analysis of the patients’ tissue in NCKUH, we found that CASZ1 is highly expressed in epithelial ovarian cancer. Furthermore, according to epithelial ovarian cancer patients’ clinical data, the patients with higher expression of CASZ1 showed worse prognosis. These results are apparently contrary to the results of neuroblastoma studies. Because of the association with CASZ1 and epithelial ovarian cancer is still unknown, we characterized the role of this gene in epithelial ovarian cancer. First, the major aim was to validate the connection between the high expression level of CASZ1 and patients’ clinical prognosis. Second, to investigate the functional role of CASZ1 in malignant behavior of epithelial ovarian cancer cells. Finally, we determined the biological characteristic of CASZ1 through animal study. According to our univariate analysis, higher CASZ1 level is significantly correlated with decreased surviving and progression free survival. In addition, patients with both high expression of CASZ1 and CA125 had the worst prognosis. In conclusion, we demonstrated that higher expression of CASZ1 level is correlated with an aggressive epithelial ovarian cancer (EOC) phenotype and may contribute to poor prognosis. Determination of prognostic level of CASZ1 can be clinically useful in identifying highly-risky EOC patients for a more aggressive adjuvant therapy.
The results of this study might enable us to understand more about CASZ1 in epithelial ovarian cancer and might therefore improve therapeutic outcome of ovarian cancer patients in the future.

[1] Chen, V. W., B. Ruiz, J. L. Killeen, T. R. Coté, X. C. Wu, C. N. Correa and H. L. Howe
(2003). "Pathology and classification of ovarian tumors." Cancer 97(S10): 2631-2642.
Christine, K. S. and F. L. Conlon (2008).
[2] Standards, Options and Recommendations. Clinical practice guidelines for cancer care
from the French National Federation of Cancer (FNCLCC). Ovarian cancer. Bri J
Cancer 2001; 84(Suppl 2):18-23.
[3] Benedet JL, Bender H, Jones H 3rd, Ngan HY, Pecorelli S. FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. Int J Gynecol Obstet 2000; 70:209-262.
[4] Berek J.S.: Novak's Gynecology, 13th ed. Philadelphia, Lippincott Williams and
Wilkins, 2002: 2145-1306.
[5] Omura GA, Brady MF, Homesley HD, et al. Long-term follow-up and prognostic
factor analysis in advanced ovarian carcinoma: the Gynecologic Oncology Group
experience. J Clin Oncol 1991; 9:1138-1150.
[6] Houwelingen JC, ten Bokkel Huinink WW, van der Burg ME, et al. Predictability
of the survival of patients with advanced ovarian cancer. J Clin Oncol 1989; 7:769-
773.
[7] Neijt JP, ten Bokkel Huinink WW, van der Burg ME, et al. Long-term survival in
ovarian cancer. Mature data from The Netherlands Joint Study Group for Ovarian
Cancer. Eur J Cancer 1991; 27:1367-1372.
[8] Hoskins WJ, Bundy BN, Thigpen JT, et al. The influence of cytoreductive surgery on
recurrence-free interval and survival in small-volume stage III epithelial ovarian
cancer: a Gynecologic Oncology Group study. Gynecol Oncol 1992; 47:159-166.
[9] Thigpen T, Brady MF, Omura GA, et al. Age as a prognostic factor in ovarian
carcinoma. The Gynecologic Oncology Group experience. Cancer 1993; 71(2 Suppl):
606-614.
[10] Liu, Z., X. Yang, F. Tan, K. Cullion and C. J. Thiele (2006). "Molecular cloning and
characterization of human< i> Castor</i>, a novel human gene upregulated during cell
differentiation." Biochemical and biophysical research communications 344(3):
834-844.
[11] Christine, K. S. and F. L. Conlon (2008). "Vertebrate CASTOR is required for
differentiation of cardiac precursor cells at the ventral midline." Developmental cell
14(4): 616-623.
[12] Bast, R. C., Jr., Feeney, M., Lazarus, H., Nadler, L. M., Colvin, R. C., and Knapp, R.
C. (1981) J. Clin. Invest. 68, 1331–1337
[13] O’Brien TJ, Beard JB, Underwood LJ, Shigemasa K. (2002). The CA125 gene: a
newly discovered extension of the glycosylated N-terminal domain doubles the size of
this extracellular superstructure.Tumour Biol 23: 154–169.
[14] Baron AT, Boardman CH, Lafky JM, Rademaker A, Liu D, Fishman DA et al. (2005).
Soluble epidermal growth factor receptor (sEGFR) [corrected] and cancer antigen 125
(CA125) as screening and diagnostic tests for epithelial ovarian cancer. Cancer
Epidemiol Biomarkers Prev 14: 306–318.
[15] Rosenthal AN, Menon U, Jacobs IJ. (2006). Screening for ovarian cancer. Clin Obstet
Gynecol 49: 433–447.
[16] Bast RC Jr, Xu FJ, Yu YH, Barnhill S, Zhang Z, Mills GB. CA125: the past and the future. Int J Biol Markers 1998;13:179–187.
[17] Liu, Z., X. Yang, Z. Li, C. McMahon, C. Sizer, L. Barenboim-Stapleton, V.
Bliskovsky, B. Mock, T. Ried and W. London (2011). "CASZ1, a candidate
tumor-suppressor gene, suppresses neuroblastoma tumor growth through
reprogramming gene expression." Cell Death & Differentiation 18(7): 1174-1183.
[18] Ruda JM, Beus KS, Hollenbeak CS, Wilson RP, Stack Jr BC. (2006).The effect of
single agent oral fusaric acid (FA) on the growth of subcutaneously xenografted SCC-1
cells in a nude mouse model.Invest New Drugs 24: 377–381.
[19] Fischer JE, Bachman LM, Jaeschke R. A readers' guide to the interpretation of
diagnostic test properties: clinical example of sepsis.Intensive Care Med 2003; 29:
1043–51.