摘要
卵巢恶性肿瘤是女性生殖系统中最常见的三大恶性肿瘤之一,病死率居妇科肿瘤之首位。其中40%-50%为卵巢浆液性囊腺癌(Ovary serous cystadenocarcinoma,OSC),最为常见。卵巢癌的早期诊断率不高,80%的患者初诊时已是晚期,预后较差,5年生存率仅为20%左右;而I期卵巢上皮性癌的5年生存率可达80-90%。早期诊断是卵巢癌防治中的关键。有效的肿瘤标志物能够提高卵巢癌的诊断率,改善预后。
本实验应用二维液质联用技术鉴定卵巢浆液性囊腺癌组织与卵巢交界性浆液腺瘤组织的差异表达蛋白谱,鉴定出的96个差异蛋白中,有83个差异蛋白表达上调;13个差异蛋白表达下调。这些差异蛋白主要包括细胞骨架蛋白、伴侣蛋白、细胞外基质蛋白、参与物质及能量代谢的酶类、信号转导、细胞周期、转录及翻译相关蛋白、免疫调节因子以及其他参与卵巢癌发生、发展、转移相关蛋白。
从中筛选出一些关键蛋白:玻联蛋白、底板反应蛋白、热休克蛋白家族、蛋白质二硫化异构酶A3、抑制素、簇蛋白、组蛋白H2Ax、骨膜蛋白、纤连蛋白、核仁蛋白、组织蛋白酶D、核心蛋白聚糖等。经进一步临床验证后有望成为高敏感性、高特异性的卵巢癌肿瘤标志物,将对卵巢癌的发病机制阐述、诊断、治疗及预后预测有重要意义。
[Objective] Ovarian cancer is the leading cause of death from gynecologic malignancy. The diagnosis rate for early- stage disease is low,and prognostic is poor.This study used differential-display proteomics technology to detect the tumor marker of ovarian cancer .
[Method] Using two dimensional liquid chromatography MS/MS (2-D LC-MS|MS) technology, we detected six ovary serous cystadenocarcinoma tissue samples(CA set) and six ovary borderline serous cystadenoma tissue samples(IN set),and obtain a protein expression reference of ovarian cancer, can potentially screen the specific ovarian cancer markers.
[Rwsults] There are 96 differential expression protein identifications screened between CA set and IN set. 83 differential proteins are overexpression, while 13 differential proteins are down-expression. These differential proteins mainly include cytoskeletal protein、molecular chaperones、extracellular matrix protein、the proteins contributed to signal transduction、cell cycle regulation、transcription、translation、immunoloregulationand energy metabolism enzymes.
[Conclusion]
1.This study use 2-D LC-MS|MS technique detect tissue samples of ovary serous cystadenocarcinoma patients and ovary borderline serous cystadenoma patients . The method is efficient, repeatability, and provide a valuable resource in study on differential protein expression of human ovarian cancer.
2. Of these differential expression protein identifications ,molecular chaperones、extracellular matrix protein , (especially glycoprotein)、the proteins contributed to signal transduction、cell cycle regulation、transcription、translation play more important roles in carcinogenesis、advancement and invasion of ovarian cancer.
3.Here we obtain some differential proteins that play key roles: vitronectin、spondin-1、heat-shock protein family、protein disulfide isomerase A3、protein disulfide-isomerase A3、prohibitin、clusterin、histone H2A.x、isoform 1 of periostin、fibromodulin、nucleolin、cathepsin D、decorin、nucleolin,etc. They could be potential tumor markers of ovarian cancer after further clinical verification, play important roles in revealing pathogenesis、diagnosis, novel treatment and prognosis evaluation of ovary cancer.
引文
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