原创力文档the proteomics of colorectal cancer identification of a protein signature associated with prognosis大肠癌的蛋白质组学鉴定蛋白质的签名与预后有关.pdfVIP
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the proteomics of colorectal cancer identification of a protein signature associated with prognosis大肠癌的蛋白质组学鉴定蛋白质的签名与预后有关
The Proteomics of Colorectal Cancer: Identification of a
Protein Signature Associated with Prognosis
Donna O’Dwyer, Lynda D. Ralton, Aisling O’Shea, Graeme I. Murray*
Department of Pathology, University of Aberdeen, Aberdeen, United Kingdom
Abstract
Colorectal cancer is one of the commonest types of cancer and there is requirement for the identification of prognostic
biomarkers. In this study protein expression profiles have been established for colorectal cancer and normal colonic mucosa
by proteomics using a combination of two dimensional gel electrophoresis with fresh frozen sections of paired Dukes B
colorectal cancer and normal colorectal mucosa (n = 28), gel image analysis and high performance liquid chromatography–
tandem mass spectrometry. Hierarchical cluster analysis and principal components analysis showed that the protein
expression profiles of colorectal cancer and normal colonic mucosa clustered into distinct patterns of protein expression.
Forty-five proteins were identified as showing at least 1.5 times increased expression in colorectal cancer and the identity of
these proteins was confirmed by liquid chromatography–tandem mass spectrometry. Fifteen proteins that showed
increased expression were validated by immunohistochemistry using a well characterised colorectal cancer tissue
microarray containing 515 primary colorectal cancer, 224 lymph node metastasis and 50 normal colonic mucosal samples.
The proteins that showed the greatest degree of overexpression in primary colorectal cancer compared with normal colonic
mucosa were heat shock protein 60 (p,0.001), S100A9 (p,0.001) and translationally controlled tumour protein (p,0.001).
Analysis of proteins individually identified 14-3-3b as a prognostic biomarker (x2 = 6.218, p = 0.013, HR = 0.639
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