Discovery of serum biomarkers implicated in the onset and progression of serous ovarian cancer in a rat model using iTRAQ technique
Discovery of serum biomarkers implicated in the onset and progression of serous ovarian cancer in a rat model using iTRAQ technique
复制标题
使用 iTRAQ 技术在大鼠模型中发现与浆液性卵巢癌发病和进展有关的血清生物标志物
DOI：
10.1016/j.ejogrb.2012.06.031
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发表时间：
2012-11-01
影响因子：
2.6
通讯作者：
Xu, Congjian
中科院分区：
文献类型：
--
作者：
Huang, Yiping;Zhang, Xiaoyan;Xu, Congjian
目的：上皮性卵巢癌（EOC）是最致命的妇科恶性肿瘤，早期肿瘤检测是提高EOC生存率的最有希望的方法。本研究的目的是确定卵巢癌发生的生物标志物。研究设计：为了模拟人类卵巢癌的发病和进展，我们通过将7，12-二甲基苯并蒽（DMBA）涂层的丝绸布条植入卵巢建立了卵巢肿瘤的大鼠模型。使用iTRAQ结合二维液相色谱和串联质谱法分析了在基线、DMBA治疗后12周和24周从携带浆液性卵巢癌（SOC）的大鼠和从对照组收集的血清。用ProteinPilot软件分析数据以进行肽匹配、蛋白质鉴定和蛋白质定量。结果：DMBA治疗32周后，卵巢肿瘤的累积发病率达到75%，与对照组相比，差异表达蛋白的经典通路和生物学相互作用网络明显增加。在所有肿瘤中，94%是EOC，51%的EOC病例是SOC。总共鉴定了225种独特的非冗余蛋白质，置信度为95%。其中27个差异表达蛋白在SOC的早期或晚期癌变过程中显著上调或下调，15个蛋白与卵巢癌的发生有关，其中12个蛋白为首次发现，包括MMRN 1、SERPINC 1、TLN 1、AHSG、PLC、APOA 2、HPX、APOC 1、APOC 2、FERMT 3、FETUB和HBB。这些差异表达蛋白的发现为了解卵巢癌动态致癌过程的分子机制提供了有价值的线索。这些蛋白质可用作早期检测、疾病监测和治疗靶点的诊断生物标志物。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
Objective: Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, and early tumor detection is the most promising approach for improving the EOC survival rate. The goal of this study was to identify the biomarkers underlying ovarian carcinogenesis.Study design: To mimic the onset and progression of human ovarian cancer, we established a rat model of ovarian neoplasm by implanting 7,12-dimethylbenz(a)anthracene (DMBA)-coated silk cloth strips onto the ovaries. Sera collected from rats bearing serous ovarian carcinoma (SOC) at baseline, 12 and 24 weeks after DMBA treatment and from controls were analyzed using iTRAQ combined with two-dimensional liquid chromatography and tandem mass spectrometry. The data were analyzed with ProteinPilot software for peptide matching, protein identification, and protein quantitation. Ingenuity pathway analysis software was used to identify the canonical pathways and biological interaction networks of differentially expressed proteins.Results: The cumulative ovarian tumor incidence rate reached 75% at 32 weeks after DMBA treatment. Out of all tumors, 94% were EOC, and 51% of the EOC cases were SOC. A total of 225 unique, non-redundant proteins were identified with 95% confidence. Twenty-seven differentially expressed proteins were significantly up- or down-regulated during the early or advanced carcinogenesis of SOC. Fifteen proteins were previously reported to be involved in ovarian cancer, and 12 proteins, including MMRN1, SERPINC1, TLN1, AHSG, PLC, APOA2, HPX, APOC1, APOC2, FERMT3, FETUB and HBB, were identified for the first time in our study.Conclusion: The discovery of these differentially expressed proteins provides valuable clues for understanding the molecular mechanism underlying the dynamic carcinogenic process of ovarian cancer. These proteins could be used as diagnostic biomarkers for early detection, disease monitoring and therapeutic targets. (C) 2012 Elsevier Ireland Ltd. All rights reserved.