Mass Spectrometry-Based Study of the Plasma Proteome in a Mouse Intestinal Tumor Model

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• 作者：Kenneth E. Hung ; Alvin T. Kho ; David Sarracino ; Larissa Georgeon Richard ; Bryan Krastins ; Sara Forrester ; Brian B. Haab ; Isaac S. Kohane ; Raju Kucherlapati
• 刊名：Journal of Proteome Research
• 出版年：2006
• 出版时间：August 2006
• 年：2006
• 卷：5
• 期：8
• 页码：1866 - 1878
• 全文大小：749K
• 年卷期：v.5,no.8(August 2006)
• ISSN：1535-3907

文摘

Early detection of cancer can greatly improve prognosis. Identification of proteins or peptides in thecirculation, at different stages of cancer, would greatly enhance treatment decisions. Mass spectrometry(MS) is emerging as a powerful tool to identify proteins from complex mixtures such as plasma thatmay help identify novel sets of markers that may be associated with the presence of tumors. To examinethis feature we have used a genetically modified mouse model, Apc^Min, which develops intestinal tumorswith 100% penetrance. Utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS), weidentified total plasma proteome (TPP) and plasma glycoproteome (PGP) profiles in tumor-bearingmice. Principal component analysis (PCA) and agglomerative hierarchial clustering analysis revealedthat these protein profiles can be used to distinguish between tumor-bearing Apc^Min and wild-typecontrol mice. Leave-one-out cross-validation analysis established that global TPP and global PGP profilescan be used to correctly predict tumor-bearing animals in 17/19 (89%) and 19/19 (100%) of cases,respectively. Furthermore, leave-one-out cross-validation analysis confirmed that the significantdifferentially expressed proteins from both the TPP and the PGP were able to correctly predict tumor-bearing animals in 19/19 (100%) of cases. A subset of these proteins was independently validated byantibody microarrays using detection by two color rolling circle amplification (TC-RCA). Analysis ofthe significant differentially expressed proteins indicated that some might derive from the stroma orthe host response. These studies suggest that mass spectrometry-based approaches to examine theplasma proteome may prove to be a valuable method for determining the presence of intestinal tumors.