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卵巢癌发生过程中血清蛋白质组谱的改变。

Alterations in the serum proteome profile during the development of ovarian cancer.

机构信息

Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.

Department of Obstetrics and Gynecology, Qianfoshan Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.

出版信息

Int J Oncol. 2014 Dec;45(6):2495-501. doi: 10.3892/ijo.2014.2675. Epub 2014 Sep 25.

Abstract

Ovarian cancer causes more deaths than any other malignant tumor of the female reproductive system. This is because the condition usually goes undetected until the late stages. The purpose of the present study is to identify alterations in the serum proteome profile during the development of ovarian cancer and to provide an experimental basis for discovering new and valuable serum biomarkers for the early detection of ovarian carcinoma. Surface-enhanced laser desorption/ionization-time of flight (SELDI-TOF-MS) was used to profile changes in the serum proteome of Fischer 344 rats with ovarian cancer during the progress of tumor development. Sera were collected from the rats on day A (1 week before injection of tumor cells), day B (4 weeks after injection), and day C (6 weeks after injection). Each sample was subjected to SELDI-TOF-MS testing. Peak detection and alignment and selection of peaks with the highest discriminatory power were performed using proteinchip biomarker software. Decision tree analyses were performed using biomarker pattern software. Finally, 3 peaks were found to be the most valuable ones (3759, 4659 and 9318 Da). The expression frequency of m/z 3759-Da peaks was downregulated and another two frequencies (4659 and 9318 Da) were upregulated, and the levels of expression of these three proteins showed the same tendency as the expression frequency during the development of ovarian cancer. The total accuracy rate of diagnosis at 4 and 6 weeks post-injection was 94.7 and 97.3%, respectively. Profiling the serum proteome changes during the process of the cancer development using SELDI-TOF-MS may provide useful information regarding carcinogenesis and facilitate discovery of novel serum biomarkers for early detection.

摘要

卵巢癌是女性生殖系统恶性肿瘤中导致死亡人数最多的癌症。这是因为这种疾病通常在晚期才被发现。本研究的目的是鉴定卵巢癌发展过程中血清蛋白质组谱的变化,并为发现新的有价值的血清生物标志物以用于卵巢癌的早期检测提供实验依据。采用表面增强激光解吸电离飞行时间(SELDI-TOF-MS)技术对卵巢癌发展过程中弗氏佐剂雌性 Fischer 344 大鼠血清蛋白质组谱的变化进行了分析。从注射肿瘤细胞前一周的第 A 天(day A)、注射后 4 周的第 B 天(day B)和注射后 6 周的第 C 天(day C)收集大鼠血清。每个样本均进行 SELDI-TOF-MS 检测。使用蛋白芯片生物标志物软件进行峰检测、对齐和选择具有最高鉴别力的峰。使用生物标志物模式软件进行决策树分析。最终发现 3 个峰最有价值(3759、4659 和 9318 Da)。m/z 3759-Da 峰的表达频率下调,另外两个频率(4659 和 9318 Da)上调,这三种蛋白质的表达水平与卵巢癌发展过程中的表达频率表现出相同的趋势。注射后 4 周和 6 周的总诊断准确率分别为 94.7%和 97.3%。采用 SELDI-TOF-MS 对癌症发展过程中血清蛋白质组变化进行分析可能为致癌作用提供有用信息,并有助于发现新的血清生物标志物用于早期检测。

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