Extensive quantitative remodeling of the proteome between normal colon tissue and adenocarcinoma

Molecular Systems Biology

Jacek R Wiśniewski¹  Paweł Ostasiewicz¹  Kamila Duś¹  Dorota F Zielińska¹  Florian Gnad¹ 

[1] Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Martinsried, Germany

关键词: colon cancer;    FASP;    FFPE tissue;    microdissection;    quantitative proteomics;   

DOI  :  10.1038/msb.2012.44

来源: Wiley

【 摘 要 】

Abstract

We report a proteomic analysis of microdissected material from formalin-fixed and paraffin-embedded colorectal cancer, quantifying >7500 proteins between patient matched normal mucosa, primary carcinoma, and nodal metastases. Expression levels of 1808 proteins changed significantly between normal and cancer tissues, a much larger fraction than that reported in transcript-based studies. Tumor cells exhibit extensive alterations in the cell-surface and nuclear proteomes. Functionally similar changes in the proteome were observed comparing rapidly growing and differentiated CaCo-2 cells. In contrast, there was minimal proteomic remodeling between primary cancer and metastases, suggesting that no drastic proteome changes are necessary for the tumor to propagate in a different tissue context. Additionally, we introduce a new way to determine protein copy numbers per cell without protein standards. Copy numbers estimated in enterocytes and cancer cells are in good agreement with CaCo-2 and HeLa cells and with the literature data. Our proteomic data set furthermore allows mapping quantitative changes of functional protein classes, enabling novel insights into the biology of colon cancer.

Synopsis

In-depth proteomic analysis of microdissected colorectal cancer identifies extensive alterations in the cell-surface and nuclear proteomes between normal mucosa and adenocarcinoma, but observes strikingly little proteomic change between cancer and metastases.

• First large-scale proteomic analysis of microdissected tissue from archival formalin-fixed and paraffin-embedded material.
• Quantitation of 7576 proteins between patient-matched samples of normal colonic mucosa, primary cancer, and nodal metastasis.
• Expression levels of 1808 proteins changed significantly between normal and cancer tissues.
• Total Protein Approach (TPA)—a new way to determine protein copy numbers per cell without protein standards.

【 授权许可】

CC BY-NC-SA   
Copyright © 2012 EMBO and Macmillan Publishers Limited

Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.