Ott Helmut W, Lindner Herbert, Sarg Bettina, Mueller-Holzner Elisabeth, Abendstein Burkhard, Bergant Anton, Fessler Siegfried, Schwaerzler Peter, Zeimet Alain, Marth Christian, Illmensee Karl
Department of Gynecology and Obstetrics, University Hospital of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
Cancer Res. 2003 Nov 1;63(21):7507-14.
Ovarian cancer remains still associated with poor prognosis because it is diagnosed predominantly at advanced stages. Ovarian-specific tumor markers do not yet exist for early detection of the disease. At the search of diagnostic markers for ovarian cancer, proteomic-based approaches have focused on novel investigations of neoplastic processes in tumor patients. Cystic fluids of malignant and benign ovarian tumors and serum from the corresponding patients were collected and processed for two-dimensional gel electrophoresis. Proteins were visualized on the gels by silver staining. At the low molecular mass level between 10 and 20 kDa, selected protein spots were additionally processed for nanospray mass spectrometry and partial amino acid sequencing. For protein identification, the sequencing results were compared with computer information from a protein data bank. Protein patterns from cystic fluids of ovarian carcinomas differed significantly from those of benign cysts and revealed additional polypeptides at low molecular mass level between 10 and 20 kDa. Protein patterns from serum of patients with malignant ovarian tumors also contained additional polypeptides between 10 and 20 kDa that were not detected in serum from patients with benign cysts. The additional proteins in serum were present in similar electrophoretic positions compared with those found in the cystic fluid of the corresponding ovarian carcinomas. Protein spots in the range of 10-20 kDa were selected for partial amino acid sequencing. Two protein spots were identified as calgranulin A and three spots as calgranulin B. Either both proteins or only calgranulin A or B were present in cystic fluid from ovarian carcinomas and serum of the corresponding patients. These two proteins were absent or not detectable in fluid from benign ovarian cysts and in serum from those patients. Our investigations concerning protein patterns in cystic fluid of malignant and benign ovarian tumors provide new information about alterations in protein synthesis linked to neoplastic events of the ovary. With the proteomic strategy, new tumor markers are characterized and may serve for diagnostic purposes of patients with ovarian cancer.
卵巢癌的预后仍然较差，因为其诊断时大多已处于晚期。目前尚无用于早期检测该疾病的卵巢特异性肿瘤标志物。在寻找卵巢癌诊断标志物的过程中，基于蛋白质组学的方法主要聚焦于对肿瘤患者肿瘤发生过程的新研究。收集了恶性和良性卵巢肿瘤的囊液以及相应患者的血清，并进行二维凝胶电泳处理。通过银染使凝胶上的蛋白质可视化。在10至20 kDa的低分子量水平，对选定的蛋白质斑点进行了额外的纳喷雾质谱分析和部分氨基酸测序。为了鉴定蛋白质，将测序结果与蛋白质数据库中的计算机信息进行比较。卵巢癌囊液的蛋白质图谱与良性囊肿的蛋白质图谱有显著差异，在10至20 kDa的低分子量水平显示出额外的多肽。恶性卵巢肿瘤患者血清的蛋白质图谱在10至20 kDa之间也含有良性囊肿患者血清中未检测到的额外多肽。与相应卵巢癌囊液中发现的蛋白质相比，血清中的额外蛋白质在相似的电泳位置出现。选择10 - 20 kDa范围内的蛋白质斑点进行部分氨基酸测序。两个蛋白质斑点被鉴定为钙粒蛋白A，三个斑点被鉴定为钙粒蛋白B。这两种蛋白质或仅钙粒蛋白A或B存在于卵巢癌囊液和相应患者的血清中。在良性卵巢囊肿的囊液和这些患者的血清中，这两种蛋白质不存在或无法检测到。我们对恶性和良性卵巢肿瘤囊液中蛋白质图谱的研究为与卵巢肿瘤事件相关的蛋白质合成改变提供了新信息。通过蛋白质组学策略，鉴定出了新的肿瘤标志物，可用于卵巢癌患者的诊断。
