卵巢癌病人化療反應及其預後的生物標記

Abstract

卵巢癌的致死率高居婦科癌症的首位。由於難以早期診斷，通常診斷時都為晚期且容易復發。五年存活率約20-30%，依期別分別為80%，65%，30%與15%。診斷包括完整了理學檢查、影像學評估、腫瘤生化指標的檢驗(例如 CA-125, CA-199, HE4)和(或)消化道檢查(胃鏡及大腸鏡，以排除腸胃道轉移腫瘤)。最主要的診斷與治療方式是完整的減積手術(debulking surgery)之後追加化學治療。即使是完整的手術與化學治療(taxol+carboplatin)，早期癌症也有20%的復發率，而初診斷已為晚期的病人則復發機會更高。有些病人對platinum-based的化學治療反應不好，需要用到第二線以後的用藥，但效果都不佳，其疾病的預後也較差。而手術、復發與化學治療都會嚴重影響病人的生活品質。目前針對卵巢癌相關的生物標記研究與預後的關係，都沒有令人滿意的答案。為了增加對疾病的了解與發展新的治療藥物，我們希望利用免疫染色合併微陣列分析基因表現及應用生物資訊統計方法，來評估和卵巢癌相關生物標記及和臨床的相關性，並進一步分析這些特定基因與蛋白質的表現量加以確認並尋找與預後與化學治療效果的相關生物標記。本研究結果將有助找出對卵巢癌病人化療反應及其預後的相關性，對未來卵巢癌病人的治療提供新的策略。

According to the 2011 annual cancer registry report in Taiwan, epithelial ovarian cancer (EOC) ranked eighth in cancer-related death and 1240 women was diagnosed in 2011 with an incidence 8.3 per 100000 women. Ovarian cancer, especially epithelial ovarian carcinoma (EOC), has become an extremely important disease in recent years because it has the highest mortality rate of all gynecological malignancies [2,3,21]. with an overall 5-year survival rate of only 20-30% [2]. It became a more and more important disease in recent years [18,27] and the incidence of ovarian cancer also increased in recent year in Taiwan. Initial evaluation for these patients includes a thorough history and physical examination, imaging studies, assessment of tumor markers (CA-125, CA-199, HE4), and/or colonoscopy and upper panendoscopy [23]. The lack of symptoms, difficulties in early diagnosis, insufficient accurate tumor markers, and lack of information about ovarian tumor biology contribute to the poor prognosis in ovarian cancer patients [9]. The prognostic parameters for ovarian carcinomas are tumor stage, histologic subtype, degree of malignancy, and residual tumor after surgical treatment [24,29]. These factors present an incomplete picture of the tumor biology of ovarian cancer and are frequently interrelated [26]. For these reasons, many patients may be delay diagnosed. Thus, the identification of new biologic factors predictive of individual disease course and prognosis would be extremely useful. From the above-mentioned data, ovarian cancer indeed is a disease that should be respected it in Taiwan. We used immunohistochemical staining combined with tissue microarray for evaluation of gene expression;combined with bioformatics with clinicopathological data in search of biomarkers related to chemotherapy response and disease prognosis