利用蛋白質體學技術觀察子宮內膜異位症患者血清中蛋白質濃度的變化

子宮內膜細胞因異位到子宮外並且在子宮以外的部位附著與增生稱之為子宮內膜異位，子宮內膜異位症是造成生育年齡婦女不孕的主要原因之一。目前臨床上所使用的方法是以腹腔鏡手術方式進行診斷，然而，腹腔鏡是一種具有高侵入性的一種診斷方式，故本研究的目的在於以蛋白質體學的研究方法，由血清檢體中，搜尋 ?在對照組與患者之間具有差異的蛋白質，並以大規模的血清篩檢，以釐清是否可作為子宮內膜異位症的血清診斷指標，以期開發低侵入性的子宮內膜異位症之血清診斷方法，取代腹腔鏡診斷法，降低病患所須承擔的風險與大量的醫療花費。本研究收集的血清檢體共有 237例，分為五組：對照組 (24例 )、懷孕組 (31例 )、卵巢骨盆性子宮內膜異位症組 (43例 )、子宮本體子宮內膜異位症 (子宮肌腺症 )組(10例 )、已接受 GnRH analog治療之子宮內膜異位症組 (90例 )。血清檢體經處理後，首先進行一維及二維電泳分離及蛋白質比對分析，結果顯示在對照組與卵巢骨盆性子宮內膜異位症組中，發現有多種蛋白質出現差異表現，經選出其中 α1-antitrypsin， haptoglobin-1，serotransferrin進行點狀墨點法於大規模的血清檢體中進一步比較篩選確認 α1-antitrypsin的表現量，在對照組與卵巢骨盆性子宮內膜異位症組血清中，後者有顯著增加的現象，而在西方墨點法的結果也看到相同的趨勢，最後，利用接受者特徵曲線估計 α1- antitrypsin在血清中的診斷閾值。以生物統計學法在我們取樣的血清檢體中定量並比較 α1-antitrypsin及癌腫瘤血清標記 CA125用於子宮內膜異位症診斷之敏感性與專一性。此研究提供了尋找血清診斷標記的方法並探討其可行性。依此研究平台，選出數個目標蛋白質，設計蛋白質晶片，作為子宮內膜異位症之診斷試劑，早期發現，同時也能改善治療的黃金時間與方式，而得以預防子宮內膜異位症的發生及其帶來的併發症。整體而言，不只是醫學上的進步，更為未來的婦女帶來一大福祉。

Endometriosis is a disease characterized by the presence of endometrial tissue of ectopic sites. The etiology of endometriosis is believed to be the dissemination of endometrial cells in the peritoneal cavity through retrograde menstruation. Endometriosis is the main cause of infertility in women at reproductive age. However, there is no efficient and low invasive procedure for diagnosis, unless laparoscopy or laparotomy, the invasive operation is applied to confirm the occurrence of endometriosis. This study aims to identify the potential serum markers for endometriosis diagnosis using proteomic approaches. By monitoring the aberrant protein expression in endometriosis compared to the controls, several different protein expressions have been identified including α1-antitrypsin, serotransferrin, haptoglobin-1. We then use the serum samples collected from 237 subjects grouped as: (1) control (n=24), (2) pregnant (n=31), (3) adenomyosis (n=10), (4) ovarian and pelvic endometriosis (n=43) and (5)endometriosis following GnRH analog treatment (n=90) by immuno-dot blot and western blot for analysis to confirm the specificity and sensitivity of the candidate protein with endomtriosis. Our data showed that α1-antitrypsin was significantly expressed in sera of women with endometriosis. Further statistics analysis indicated that α1-antitrypsin could be a potential marker for diagnosis of endometriosis. Identification of serum marker is substantial for disease diagnosis and the follow-up treatment. This proteomic approach will progress for the development of diagnosis tool and therapeutic strategies for endometriosis.

Studies of Differential Expressions of Serum Proteins in Patients with Endometriosis Using Proteomic Approaches