Evidence map›Paper›PMID 26984550›Full record

ArticleJournal of gastroenterology2016

Carcinoma of the colon and rectum with deregulation of insulin-like growth factor 2 signaling: clinical and molecular implications.

Djeda Belharazem, Julia Magdeburg, Ann-Kristin Berton, Li Beissbarth, Christian Sauer, Carsten Sticht, Alexander Marx, Ralf Hofheinz, Stefan Post, Peter Kienle and 1 more

Abstract read
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In one paragraph

Article in Journal of gastroenterology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

18 citing papers in PubMed, 27 citations in OpenAlex.

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  15. Loss ofCancer research · 2017
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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

11 authors at 5 institutions in 1 country.

Djeda BelharazemInstitute of Pathology, University Medical Center Mannheim, University of Heidelberg, Heidelberg, Germany.
Julia MagdeburgDepartment of Surgery, University Medical Center Mannheim, University of Heidelberg, Heidelberg, Germany.
Ann-Kristin BertonInstitute of Pathology, University Medical Center Mannheim, University of Heidelberg, Heidelberg, Germany.
Li BeissbarthInstitute of Pathology, University Medical Center Göttingen, Robert-Koch-Str 40, 37075, Göttingen, Germany.
Christian SauerInstitute of Pathology, University Medical Center Mannheim, University of Heidelberg, Heidelberg, Germany.
Carsten StichtMedical Research Center (ZMF), University Medical Center Mannheim, University of Heidelberg, Heidelberg, Germany.
Alexander MarxInstitute of Pathology, University Medical Center Mannheim, University of Heidelberg, Heidelberg, Germany.
Ralf HofheinzMedical Clinic, University Medical Center Mannheim, University of Heidelberg, Heidelberg, Germany.
Stefan PostDepartment of Surgery, University Medical Center Mannheim, University of Heidelberg, Heidelberg, Germany.
Peter KienleDepartment of Surgery, University Medical Center Mannheim, University of Heidelberg, Heidelberg, Germany.
Philipp StröbelInstitute of Pathology, University Medical Center Göttingen, Robert-Koch-Str 40, 37075, Göttingen, Germany. philipp.stroebel@med.uni-goettingen.de.
Heidelberg University · DEUniversity Medical Centre Mannheim · DEUniversity Hospital Heidelberg · DEUniversitätsmedizin Göttingen · DEUniversity of Göttingen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLoss of imprinting (LOI) of the insulin-like growth factor 2 (IGF2) is an early event in the development of colorectal cancer (CRC). Whether LOI of IGF2 denotes a molecular or clinical cancer subgroup is currently unknown.

methodsTumor biopsies and paired normal mucosa from 399 patients with extensive clinical annotations were analyzed for LOI and IGF2 expression. LOI status in 140 informative cases was correlated with clinicopathologic parameters and outcome.

resultsLOI was frequent in normal mucosa and tumors and occurred throughout the large intestine. LOI was unrelated to microsatellite instability, KRAS mutation status, stage, and survival. However, CRC with LOI showed increased IGF2 protein levels and activation of AKT1. Gene expression analysis of tumors with and without LOI and knockdown of IGF2 in cell lines revealed that IGF2 induced distinct sets of activated and repressed genes, including Wnt5a, CEACAM6, IGF2BP3, KPN2A, BRCA2, and CDK1. Inhibition of AKT1 in IGF2-stimulated cells showed that the downstream effects of IGF2 on cell proliferation and gene expression were strictly AKT1-dependent.

conclusionsLOI of IGF2 is a frequent and early event in CRC that occurs both in the adenomatous polyposis coli (APC) gene-mutated and serrated route of carcinogenesis. LOI leads to overexpression of IGF2, activates IGF1R and AKT1, and is a powerful driver of cell proliferation. Moreover, our results suggest that IGF2 via AKT1 also contributes to non-canonical wnt signaling. Although LOI had no significant impact on major clinical parameters and outcome, its potential as a target for preventive and therapeutic interventions merits further investigation.

Indexed as

AdultAgedAged, 80 and overAntigens, CDBRCA2 ProteinCarcinomaCDC2 Protein KinaseCell Adhesion MoleculesCell Line, TumorColorectal NeoplasmsCyclin-Dependent KinasesEpigenesis, GeneticFemaleGene ExpressionGene Expression ProfilingGenotypeAKT1 protein, humanAntigens, CDBRCA2 ProteinCDC2 Protein KinaseCDK1 protein, humanCEACAM6 protein, humanCell Adhesion MoleculesCyclin-Dependent KinasesGPI-Linked ProteinsIGF1R protein, humanIGF2BP3 protein, humanIGF2 protein, humanInsulin-Like Growth Factor IIKRAS protein, humanProto-Oncogene Proteins c-aktProto-Oncogene Proteins p21(ras)Receptor, IGF Type 1Receptors, SomatomedinRNA-Binding ProteinsWnt-5a ProteinWNT5A protein, humanAKT1Colon cancerIGF2ImprintingWnt5a

Identifiers

PMID26984550
OpenAlexW2304456342

What OpenQuestion holds

Textmetadata
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.