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High sensitivity isoelectric focusing to establish a signaling biomarker for the diagnosis of human colorectal cancer

Overview of attention for article published in BMC Cancer, August 2016
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Title
High sensitivity isoelectric focusing to establish a signaling biomarker for the diagnosis of human colorectal cancer
Published in
BMC Cancer, August 2016
DOI 10.1186/s12885-016-2725-z
Pubmed ID
Authors

Narendra Padhan, Torbjörn E. M. Nordling, Magnus Sundström, Peter Åkerud, Helgi Birgisson, Peter Nygren, Sven Nelander, Lena Claesson-Welsh

Abstract

The progression of colorectal cancer (CRC) involves recurrent amplifications/mutations in the epidermal growth factor receptor (EGFR) and downstream signal transducers of the Ras pathway, KRAS and BRAF. Whether genetic events predicted to result in increased and constitutive signaling indeed lead to enhanced biological activity is often unclear and, due to technical challenges, unexplored. Here, we investigated proliferative signaling in CRC using a highly sensitive method for protein detection. The aim of the study was to determine whether multiple changes in proliferative signaling in CRC could be combined and exploited as a "complex biomarker" for diagnostic purposes. We used robotized capillary isoelectric focusing as well as conventional immunoblotting for the comprehensive analysis of epidermal growth factor receptor signaling pathways converging on extracellular regulated kinase 1/2 (ERK1/2), AKT, phospholipase Cγ1 (PLCγ1) and c-SRC in normal mucosa compared with CRC stage II and IV. Computational analyses were used to test different activity patterns for the analyzed signal transducers. Signaling pathways implicated in cell proliferation were differently dysregulated in CRC and, unexpectedly, several were downregulated in disease. Thus, levels of activated ERK1 (pERK1), but not pERK2, decreased in stage II and IV while total ERK1/2 expression remained unaffected. In addition, c-SRC expression was lower in CRC compared with normal tissues and phosphorylation on the activating residue Y418 was not detected. In contrast, PLCγ1 and AKT expression levels were elevated in disease. Immunoblotting of the different signal transducers, run in parallel to capillary isoelectric focusing, showed higher variability and lower sensitivity and resolution. Computational analyses showed that, while individual signaling changes lacked predictive power, using the combination of changes in three signaling components to create a "complex biomarker" allowed with very high accuracy, the correct diagnosis of tissues as either normal or cancerous. We present techniques that allow rapid and sensitive determination of cancer signaling that can be used to differentiate colorectal cancer from normal tissue.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Sweden 1 6%
Taiwan 1 6%
Unknown 14 88%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 31%
Student > Master 3 19%
Other 2 13%
Student > Ph. D. Student 2 13%
Lecturer > Senior Lecturer 1 6%
Other 2 13%
Unknown 1 6%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 5 31%
Medicine and Dentistry 4 25%
Engineering 2 13%
Computer Science 1 6%
Chemistry 1 6%
Other 1 6%
Unknown 2 13%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 August 2016.
All research outputs
#7,165,316
of 8,286,032 outputs
Outputs from BMC Cancer
#2,814
of 3,488 outputs
Outputs of similar age
#212,572
of 252,710 outputs
Outputs of similar age from BMC Cancer
#155
of 227 outputs
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