Bhattacharya, Sayantan, Mathew, George, Ruban, Ernie, Epstein, David B. A., Krusche, Andreas, Hillert, Reyk, Schubert, Walter and Khan, Michael. (2010) Toponome imaging system in situ protein network mapping in normal and cancerous colon from the same patient reveals more than five-thousand cancer specific protein clusters and their subcellular annotation by using a three symbol code. Journal of Proteome Research, Vol.9 (No.12). pp. 6112-6125. ISSN 1535-3893

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Abstract

In a proof of principle study, we have applied an automated fluorescence toponome imaging system (TIS) to examine whether TIS can find protein network structures, distinguishing cancerous from normal colon tissue present in a surgical sample from the same patient By using a three symbol code and a power of combinatorial molecular discrimination (PCMD) of 2(21) per subcellular data point in one single tissue section, we demonstrate an in situ protein network structure, visualized as a mosaic of 6813 protein clusters (combinatorial molecular phenotype or CMPs), in the cancerous part of the colon By contrast, in the histologically normal colon, TIS identifies nearly 5 times the number of protein clusters as compared to the cancerous part (32 009) By subcellular visualization procedures we found that many cell surface membrane molecules were closely associated with the cell cytoskeleton as unique CMPs in the normal part of the colon, while the same molecules were disassembled in the cancerous part, suggesting the presence of dysfunctional cytoskeleton-membrane complexes As expected, glandular and stromal cell signatures were found, but interestingly also found were potentially TIS signatures identifying a very restricted subset of cells expressing several putative stem cell markers all restricted to the cancerous tissue The detection of these signatures is based on the extreme searching depth, high degree of dimensionality and subcellular resolution capacity of TIS These findings provide the technological rationale for the feasibility of a complete colon cancer toponome to be established by massive parallel high throughput/high content TIS mapping

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry
Divisions:	Faculty of Medicine > Warwick Medical School
Journal or Publication Title:	Journal of Proteome Research
Publisher:	American Chemical Society
ISSN:	1535-3893
Official Date:	December 2010
Volume:	Vol.9
Number:	No.12
Number of Pages:	14
Page Range:	pp. 6112-6125
Identification Number:	10.1021/pr100157p
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	Klaus Tschira foundation, BMBF, Med Fak, Univ of Magdeburg, Germany
Grant number:	DFGschu627/10 1, Innovationskolleg INK15
URI:	http://wrap.warwick.ac.uk/id/eprint/4717

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