Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Eur J Cancer. 2010 Jul;46(11):2104-18. doi: 10.1016/j.ejca.2010.04.015. Epub 2010 May 22.
Serous ovarian carcinoma (SOC) is the most common subtype of epithelial ovarian cancer which remains the leading cause of death from gynaecologic malignancy. Further knowledge of the proteins involved in serous ovarian cancer may lead to new treatment targets, new markers for early detection or prognosis prediction. In this study, we applied proteomic techniques to analyse the protein expression profiles of SOC and normal ovarian epithelium tissues. Totally 54 aberrantly expressed proteins were identified using 2-DE combined with MALDI-TOF/TOF. Six of these proteins were validated by western blot. Corresponding gene expression analysis of these proteins was also performed using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). Additionally, we analysed glia maturation factor beta (GMFB) protein expression by immunohistochemistry in 246 patients with various degrees of ovarian epithelial lesions. GMFB expression in SOC was found to be significantly enhanced than that in normal epithelium, benign serous adenoma and borderline serous adenoma tissues, and was positively correlated with FIGO stage (P=0.012). High GMFB expression was associated with poor disease-free survival (P=0.010) and overall survival (P=0.003), while multivariate analysis revealed GMFB to be an independent prognostic factor for disease-free survival (P=0.026) and overall survival (P=0.006) in patients with SOC. We therefore propose that proteins identified here may be involved in the development or progression of SOC, and GMFB can be considered as a prognostic predictor for SOC patients.
浆液性卵巢癌(SOC)是最常见的上皮性卵巢癌亚型,仍是妇科恶性肿瘤死亡的主要原因。进一步了解浆液性卵巢癌中涉及的蛋白质可能会为新的治疗靶点、早期检测或预后预测的新标志物提供依据。在这项研究中,我们应用蛋白质组学技术分析 SOC 和正常卵巢上皮组织的蛋白质表达谱。通过 2-DE 联合 MALDI-TOF/TOF 共鉴定出 54 个异常表达蛋白。其中 6 个蛋白通过 Western blot 进行了验证。还通过实时定量逆转录聚合酶链反应(RT-PCR)对这些蛋白的相应基因表达进行了分析。此外,我们通过免疫组织化学法在 246 例不同程度卵巢上皮病变患者中分析了神经胶质细胞成熟因子-β(GMFB)蛋白的表达。SOC 中的 GMFB 表达明显高于正常上皮、良性浆液性腺瘤和交界性浆液性腺瘤组织,且与 FIGO 分期呈正相关(P=0.012)。GMFB 高表达与无病生存(P=0.010)和总生存(P=0.003)不良相关,而多变量分析显示 GMFB 是 SOC 患者无病生存(P=0.026)和总生存(P=0.006)的独立预后因素。因此,我们提出这里鉴定的蛋白可能参与 SOC 的发生或进展,GMFB 可作为 SOC 患者的预后预测指标。