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

Wiśniewski JR, Ostasiewicz P, Duś K, Zielińska DF, Gnad F, Mann M - Mol. Syst. Biol. (2012)

Bottom Line: 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.Our proteomic data set furthermore allows mapping quantitative changes of functional protein classes, enabling novel insights into the biology of colon cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Martinsried, Germany. jwisniew@biochem.mpg.de

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.

Show MeSH

Related in: MedlinePlus

Quantitative comparison of proteins identified in colonic mucosa, cancer, and metastasis. (A) Unsupervised hierarchical clustering of intensities of 7576 proteins for patient matching primary adenocarcinomas and adjacent normal mucosa (8 pairs) and 7 nodal metastases. (B) Distribution of protein ratios versus protein abundance.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3472694&req=5

f3: Quantitative comparison of proteins identified in colonic mucosa, cancer, and metastasis. (A) Unsupervised hierarchical clustering of intensities of 7576 proteins for patient matching primary adenocarcinomas and adjacent normal mucosa (8 pairs) and 7 nodal metastases. (B) Distribution of protein ratios versus protein abundance.

Mentions: To assess the similarities of the analyzed proteomes in a global manner, we performed unsupervised clustering, in which samples are grouped on the basis of their expression patterns (Figure 3A). All eight samples of normal mucosa clustered together. In striking contrast, cancer and nodal metastases clustered into seven patient matched pairs. In these pairs, the primary tumor had a higher similarity to its metastatic counterpart than to other tumors. To identify potential driver proteins of cancer, we first compared the intensities of detected proteins between colonic mucosa, primary cancer, and its nodal metastasis. Paired t-test was used to determine the significance of protein differences. In total, 1808 proteins were significantly (P<0.05) downregulated or upregulated in tumor tissues when compared with normal mucosa (Figure 3B; Supplementary Table 5). Changes of 762 proteins were observed at a P-value of 0.01 (Figure 3B). The same statistical analysis of our proteomics data did not identify any significant changes between the primary tumor and the nodal metastasis.


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

Wiśniewski JR, Ostasiewicz P, Duś K, Zielińska DF, Gnad F, Mann M - Mol. Syst. Biol. (2012)

Quantitative comparison of proteins identified in colonic mucosa, cancer, and metastasis. (A) Unsupervised hierarchical clustering of intensities of 7576 proteins for patient matching primary adenocarcinomas and adjacent normal mucosa (8 pairs) and 7 nodal metastases. (B) Distribution of protein ratios versus protein abundance.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472694&req=5

f3: Quantitative comparison of proteins identified in colonic mucosa, cancer, and metastasis. (A) Unsupervised hierarchical clustering of intensities of 7576 proteins for patient matching primary adenocarcinomas and adjacent normal mucosa (8 pairs) and 7 nodal metastases. (B) Distribution of protein ratios versus protein abundance.
Mentions: To assess the similarities of the analyzed proteomes in a global manner, we performed unsupervised clustering, in which samples are grouped on the basis of their expression patterns (Figure 3A). All eight samples of normal mucosa clustered together. In striking contrast, cancer and nodal metastases clustered into seven patient matched pairs. In these pairs, the primary tumor had a higher similarity to its metastatic counterpart than to other tumors. To identify potential driver proteins of cancer, we first compared the intensities of detected proteins between colonic mucosa, primary cancer, and its nodal metastasis. Paired t-test was used to determine the significance of protein differences. In total, 1808 proteins were significantly (P<0.05) downregulated or upregulated in tumor tissues when compared with normal mucosa (Figure 3B; Supplementary Table 5). Changes of 762 proteins were observed at a P-value of 0.01 (Figure 3B). The same statistical analysis of our proteomics data did not identify any significant changes between the primary tumor and the nodal metastasis.

Bottom Line: 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.Our proteomic data set furthermore allows mapping quantitative changes of functional protein classes, enabling novel insights into the biology of colon cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Martinsried, Germany. jwisniew@biochem.mpg.de

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.

Show MeSH
Related in: MedlinePlus