Protein Expression Changes in Ovarian Cancer during the Transition from Benign to Malignant
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- 作者：Sofia Waldemarson ; Morten Krogh ; Ayodele Alaiya ; Ufuk Kirik ; Kjell Schedvins ; Gert Auer ; Karin M. Hansson ; Reto Ossola ; Ruedi Aebersold ; Hookeun Lee ; Johan Malmstr枚m ; Peter James
- 刊名：Journal of Proteome Research
- 出版年：2012
- 出版时间：May 4, 2012
- 年：2012
- 卷：11
- 期：5
- 页码：2876-2889
- 全文大小：478K
- 年卷期：v.11,no.5(May 4, 2012)
- ISSN：1535-3907
文摘
Epithelial ovarian carcinoma has in general a poor prognosis since the vast majority of tumors are genomically unstable and clinically highly aggressive. This results in rapid progression of malignancy potential while still asymptomatic and thus in late diagnosis. It is therefore of critical importance to develop methods to diagnose epithelial ovarian carcinoma at its earliest developmental stage, that is, to differentiate between benign tissue and its early malignant transformed counterparts. Here we present a shotgun quantitative proteomic screen of benign and malignant epithelial ovarian tumors using iTRAQ technology with LC鈥揗ALDI-TOF/TOF and LC鈥揈SI-QTOF MS/MS. Pathway analysis of the shotgun data pointed to the PI3K/Akt signaling pathway as a significant discriminatory pathway. Selected candidate proteins from the shotgun screen were further confirmed in 51 individual tissue samples of normal, benign, borderline or malignant origin using LC-MRM analysis. The MRM profile demonstrated significant differences between the four groups separating the normal tissue samples from all tumor groups as well as perfectly separating the benign and malignant tumors with a ROC-area of 1. This work demonstrates the utility of using a shotgun approach to filter out a signature of a few proteins only that discriminates between the different sample groups.