p53自體抗體可作為婦科疾病的 診斷標記

p53 autoantibody can be used as diagnostic tumor marker for gynecological diseases

蘇家鈴(Chia-Ling Su)

指導教授 ： 陳凌雲

中山醫學大學/醫學院/生化暨生物科技研究所/碩士(2008年)

https://doi.org/10.6834/CSMU.2008.00057

摘要

子宮肌腺症、子宮肌瘤和子宮內膜異位症是女性生殖系統中常見的良性腫瘤，雖然不是造成高死亡率的疾病，但若症狀過於嚴重，則會影響患者的生活品質甚至進而影響到患者的生育能力。此外患者即使接受治療但其復發率仍偏高，有鑑於此，如能藉由抽血檢查的方式，找到能有效偵測對子宮肌腺症、子宮肌瘤和子宮內膜異位症之診斷標記，將會對患者在治療追蹤及診斷上有所助益。有相關文獻指出SEREX (Serological identification of antigen by recombinant expression cloning)的實驗方法，利用癌症患者血清中的自體抗體可辨識腫瘤相關抗原(Tumor associated antigen, TAA)來協助診斷癌症的變化或癒後追蹤的工具。本實驗室以酵素連結免疫吸附分析法篩檢IMP1、p53、p90及p16四個腫瘤相關抗原的自體抗體，在30位子宮肌腺症、子宮肌瘤和子宮內膜異位症患者血清中的表現其陽性出現率：IMP1為23.33%，p53為56.67%，p90為0%，p16為60%，結果顯示p53與p16自體抗體可作為婦科疾病診斷的標誌。為了進一步確認，本實驗將婦科疾病患者的檢體數目從30位增加到105位，而正常人檢體數也由31位增加至55位，結果顯示p53自體抗體在105位患者的陽性出現率是23.81%(p53自體抗體的陽性出現率在子宮肌腺症是26.33%、在子宮肌瘤是24.24%、在子宮內膜異位症是11.32%)。另因在正常女性中其實存在著尚未出現疾病症狀的偽陽性正常人，也因此我們以偵測30位正常人的cutoff value來分析105位婦科病患，結果是p53自體抗體的陽性出現率是59.05%(p53自體抗體的陽性出現率在子宮肌腺症是52.63%、在子宮肌瘤是66.67%、在子宮內膜異位症是30.19%)。期望未來能將p53與其它的腫瘤相關抗原(如IMP1及p16)的偵測結果進行交叉分析，以提升p53自體抗體偵測子宮肌腺症、子宮肌瘤、子宮內膜異位症的敏感度，期能以經濟、快速、方便之方式應用於不孕症門診相關患者之療效監測及診斷。

關鍵字

p53自體抗體

並列摘要

Adenomyosis, myoma, leiomyoma, endometriosis and endometrioma are the most common diseases in the female reproductive system. They do not make patients high mortality, but they were the major reason cause of female infertility. Therefore, it is important in the follow up diagnosis of above patients. Previous data had show that the SEREX (Serological identification antigen by recombinant expression cloning) method could detect the autoantibodies that can against the tumor associated antigens in the cancer patients' serum. We choose four TAA (including IMP1, p90, and p16) to screen the autoantibodies in 30 patients’ serum by ELISA. The positive rate of IMP1 were 23.33%, p53 were 56.67%, p90 were 0%, and p16 were 60 %. It seems that the p53 and p16 autoantibody posses high specificity and high sensitivity which may be a tumor marker in adenomyosis, myoma, leiomyoma, endometriosis and endometrioma. Because the specimens are too little, we increase from 30 to 105 patients' specimens and healthy individuals from 31 to 55 to confirm p53 is a useful tumor marker in gynecological patients. By (Mean+SD)cutoff value, the results show that autoantibody to p53 positive rate was 23.81% (adenomyosis was 26.33%, myoma and leiomyoma was 24.24%, and endometriosis and endometrioma was 11.32%). There are some asymptomatic patient in the 55 normal health indivudals. We try to use screen 31 normal health indivudals' cutoff value to analyze . By 31 normal health indivudals' (Mean+SD)cutoff value, the results show that autoantibody to p53 positive rate was 59.05%(adenomyosis was 52.63%, myoma and leiomyoma was 66.67%, and endometriosis and endometrioma was 30.19%).In order to increase the accuracy of positive reactors, we plan add another IMP1 and p16 autoantibody and then can cross the all results to improve accuracy in the future. The p53 autoantibody maybe can help diagnose or prognosis of the adenomyosis, myoma, leiomyoma, endometriosis and endometrioma as the tracked tool in the infertility outpatient.

並列關鍵字

p53 autoantibody

參考文獻

Ling Bai and Wei-Guo Zhu (2006). p53: Structure, Function and Therapeutic Applications. Journal of Cancer Molecules 2, 141-153.

A Dey, CS Verma and DP Lane (2008). Updates on p53: modulation of p53 degradation as a therapeutic approach. British Journal of Cancer 98, 4-8.

Amanda K. Miles, Balwir Matharoo-Ball, Geng Li Murrium Ahmad, Robert C. Rees (2006). The identification of human tumor antigens: current status and future development. Cancer Immunol Immunother 55, 996-1003.

Bossi G, Sacchi A (2007). Restoration of wild-type p53 function in human cancer: relevance for tumor therapy. Head & neck 29, 272-284.

Carlos A. Casiano, Melanie Mediavilla-Varela, and Eng M. Tan (2006). Tumor-associated antigen arrays for the serological diagnosis of cancer. Molecular & Cellular Proteomics 5, 1745-1759.