Proteomic analyses of serous and endometrioid epithelial ovarian cancers - Cases studies - Molecular insights of a possible histological etiology of serous ovarian cancer
Proteomic analyses of serous and endometrioid epithelial ovarian cancers - Cases studies - Molecular insights of a possible histological etiology of serous ovarian cancer
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DOI：
10.1002/prca.201200079
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发表时间：
2013-06-01
影响因子：
2
通讯作者：
Salzet, Michel
中科院分区：
文献类型：
--
作者：
Longuespee, Remi;Gagnon, Hugo;Salzet, Michel
卵巢上皮性癌变可能发生在卵巢间皮上皮细胞表面，也可能发生在其他器官的上皮细胞上。外源苗勒管细胞侵入卵巢环境的假设可以解释后一种情况。在这项研究中，MALDI质谱分析技术被用于提供有关这些潜在不同机制的分子见解。实验设计利用MALDI质谱分析，在其解剖学背景下建立分子疾病特征。MALDI MS谱分析用于浆液癌和子宫内膜样癌活检，以调查上皮性卵巢癌的病例。然后，我们应用生物信息学方法和鉴定策略对消化的福尔马林固定石蜡包埋组织的提取物进行LC-MS/MS分析。选取区域（卵巢浆液性腺癌、输卵管浆液性腺癌、子宫内膜样卵巢癌、良性子宫内膜和良性卵巢组织）进行提取，并进行肽消化LC-MS/MS分析。结果将良性子宫内膜与三种卵巢癌类型（浆液性卵巢腺癌、子宫内膜样卵巢腺癌和浆液性输卵管腺癌）的蛋白进行比较，为输卵管与浆液性卵巢腺癌之间可能存在的相关性提供了新的证据。在这里，我们提出了一个工作流，包括在其解剖背景下的多个组织在一个病人的比较。结论和临床意义本研究为这两种组织之间的分子相似性提供了新的见解，并为个体化患者诊断和护理提供了高度特异性的标志物评估。
Purpose Epithelial ovarian carcinogenesis may occur de novo on the surface of ovarian mesothelial epithelial cells or from cells originating in other organs. Foreign Mullerian cell intrusion into the ovarian environment has been hypothesized to explain the latter scenario. In this study, MALDI MS profiling technology was used to provide molecular insights regarding these potentially different mechanisms. Experimental design Using MALDI MS profiling, the molecular disease signatures were established in their anatomical context. MALDI MS profiling was used on serous and endometrioid cancer biopsies to investigate cases of epithelial ovarian cancer. We then applied bioinformatic methods and identification strategies on the LC-MS/MS analyses of extracts from digested formalin-fixed, paraffin-embedded tissues. Extracts from selected regions (i.e. serous ovarian adenocarcinoma, fallopian tube serous adenocarcinoma, endometrioid ovarian cancer, benign endometrium, and benign ovarian tissues) were performed, and peptide digests were subjected to LC-MS/MS analysis. Results Comparison of the proteins identified from benign endometrium or three ovarian cancer types (i.e. serous ovarian adenocarcinoma, endometrioid ovarian adenocarcinoma, and serous fallopian tube adenocarcinoma) provided new evidence of a possible correlation between the fallopian tubes and serous ovarian adenocarcinoma. Here, we propose a workflow consisting of the comparison of multiple tissues in their anatomical context in an individual patient. Conclusion and clinical relevance The present study provides new insights into the molecular similarities between these two tissues and an assessment of highly specific markers for an individualized patient diagnosis and care.