Evidence map›Paper›PMID 27562229›Full record

ArticleBMC cancer2016

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

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

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.3field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Akt3 Regulates the Tissue-Specific Response to Copaiba Essential Oil.International journal of molecular sciences · 2020
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 2 countries.

Narendra PadhanDepartment of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Dag Hammarskjöldsv 20, Uppsala, 751 85, Sweden.
Torbjörn E M NordlingDepartment of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Dag Hammarskjöldsv 20, Uppsala, 751 85, Sweden.
Magnus SundströmDepartment of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Dag Hammarskjöldsv 20, Uppsala, 751 85, Sweden.
Peter ÅkerudDepartment Surgical Sciences, Uppsala University, 751 85, Uppsala, Sweden.
Helgi BirgissonDepartment Surgical Sciences, Uppsala University, 751 85, Uppsala, Sweden.
Peter NygrenDepartment of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Dag Hammarskjöldsv 20, Uppsala, 751 85, Sweden.
Sven NelanderDepartment of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Dag Hammarskjöldsv 20, Uppsala, 751 85, Sweden.
Lena Claesson-WelshDepartment of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Dag Hammarskjöldsv 20, Uppsala, 751 85, Sweden. lena.welsh@igp.uu.se.ORCID 0000-0003-4275-2000
Uppsala University · SE

Funding

Worldwide Cancer Research 13-1295
6 · The paper itself

Abstract

backgroundThe 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.

methodsWe 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.

resultsSignaling 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.

conclusionsWe present techniques that allow rapid and sensitive determination of cancer signaling that can be used to differentiate colorectal cancer from normal tissue.

Indexed as

Biomarkers, TumorSignal TransductionBiopsyCell Line, TumorCell ProliferationColorectal NeoplasmsCSK Tyrosine-Protein KinaseErbB ReceptorsGene Expression Regulation, NeoplasticHumansIsoelectric FocusingMitogen-Activated Protein Kinase 3MutationNeoplasm StagingPhospholipase C gammaPhosphorylationBiomarkers, TumorCSK protein, humanCSK Tyrosine-Protein KinaseErbB ReceptorsMitogen-Activated Protein Kinase 3Phospholipase C gammaProto-Oncogene Proteins c-aktRibosomal Protein S6 Kinases, 70-kDasrc-Family KinasesColorectal cancerc-SRCERKIsoelectric focusingProliferationSignal transduction

Identifiers

PMID27562229
PMCPMC5000422
OpenAlexW2517603590

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.