Evidence map›Paper›PMID 24404136›Full record

ArticlePloS one2014

Clinical classification of cancer cachexia: phenotypic correlates in human skeletal muscle.

Neil Johns, Shinji Hatakeyama, Nathan A Stephens, Martin Degen, Simone Degen, Wilfried Frieauff, Christian Lambert, James A Ross, Ronenn Roubenoff, David J Glass and 2 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

50 citing papers in PubMed, 89 citations in OpenAlex.

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  13. UBR2 targets myosin heavy chain IIb and IIx for degradation: Molecular mechanism essential for cancer-induced muscle wasting.Proceedings of the National Academy of Sciences of the United States of America · 2022
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  16. REDD1 deletion attenuates cancer cachexia in mice.Journal of applied physiology (Bethesda, Md. : 1985) · 2021
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 3 countries.

Neil JohnsDepartment of Clinical and Surgical Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Shinji HatakeyamaNovartis Institutes for BioMedical Research Basel, Novartis Pharma AG, Basel, Switzerland.
Nathan A StephensDepartment of Clinical and Surgical Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Martin DegenNovartis Institutes for BioMedical Research Basel, Novartis Pharma AG, Basel, Switzerland.
Simone DegenNovartis Institutes for BioMedical Research Basel, Novartis Pharma AG, Basel, Switzerland.
Wilfried FrieauffNovartis Institutes for BioMedical Research Basel, Novartis Pharma AG, Basel, Switzerland.
Christian LambertNovartis Institutes for BioMedical Research Basel, Novartis Pharma AG, Basel, Switzerland.
James A RossDepartment of Clinical and Surgical Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Ronenn RoubenoffNovartis Institutes for Biomedical Research, Cambridge, Massachusetts, United States of America.
David J GlassNovartis Institutes for Biomedical Research, Cambridge, Massachusetts, United States of America.
Carsten JacobiNovartis Institutes for BioMedical Research Basel, Novartis Pharma AG, Basel, Switzerland.
Kenneth C H FearonDepartment of Clinical and Surgical Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Novartis (Switzerland) · CHUniversity of Edinburgh · GBNovartis (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCachexia affects the majority of patients with advanced cancer and is associated with a reduction in treatment tolerance, response to therapy, and duration of survival. One impediment towards the effective treatment of cachexia is a validated classification system.

methods41 patients with resectable upper gastrointestinal (GI) or pancreatic cancer underwent characterisation for cachexia based on weight-loss (WL) and/or low muscularity (LM). Four diagnostic criteria were used >5%WL, >10%WL, LM, and LM+>2%WL. All patients underwent biopsy of the rectus muscle. Analysis included immunohistochemistry for fibre size and type, protein and nucleic acid concentration, Western blots for markers of autophagy, SMAD signalling, and inflammation.

findingsCompared with non-cachectic cancer patients, patients with LM or LM+>2%WL, mean muscle fibre diameter was reduced by about 25% (p = 0.02 and p = 0.001 respectively). No significant difference in fibre diameter was observed if patients had WL alone. Regardless of classification, there was no difference in fibre number or proportion of fibre type across all myosin heavy chain isoforms. Mean muscle protein content was reduced and the ratio of RNA/DNA decreased in patients with either >5%WL or LM+>2%WL. Compared with non-cachectic patients, SMAD3 protein levels were increased in patients with >5%WL (p = 0.022) and with >10%WL, beclin (p = 0.05) and ATG5 (p = 0.01) protein levels were increased. There were no differences in phospho-NFkB or phospho-STAT3 levels across any of the groups.

conclusionMuscle fibre size, biochemical composition and pathway phenotype can vary according to whether the diagnostic criteria for cachexia are based on weight loss alone, a measure of low muscularity alone or a combination of the two. For intervention trials where the primary end-point is a change in muscle mass or function, use of combined diagnostic criteria may allow identification of a more homogeneous patient cohort, reduce the sample size required and enhance the time scale within which trials can be conducted.

Indexed as

PhenotypeAgedAutophagyBiomarkersBody Mass IndexCachexiaFemaleHumansInflammationMaleMiddle AgedMuscle, SkeletalNeoplasmsSignal TransductionSmad ProteinsWeight LossBiomarkersSmad Proteins

Identifiers

PMID24404136
PMCPMC3880262
OpenAlexW2073522519

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.