Evidence map›Paper›PMID 38917511›Full record

SynthesisEBioMedicine2024

Large-scale external validation and meta-analysis of gene methylation biomarkers in tumor tissue for colorectal cancer prognosis.

Tanwei Yuan, Durgesh Wankhede, Dominic Edelmann, Jakob Nikolas Kather, Katrin E Tagscherer, Wilfried Roth, Melanie Bewerunge-Hudler, Alexander Brobeil, Matthias Kloor, Hendrik Bläker and 2 more

Abstract readMeta-Analysis
In one paragraph

Synthesis in EBioMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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

7 citing papers in PubMed.

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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

12 authors.

Tanwei YuanDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.
Durgesh WankhedeDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Dominic EdelmannDivision of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Jakob Nikolas KatherElse Kroener Fresenius Center for Digital Health, Technical University Dresden, Dresden, Germany.
Katrin E TagschererInstitute of Pathology, University Medical Center Mainz, Mainz, Germany.
Wilfried RothInstitute of Pathology, University Medical Center Mainz, Mainz, Germany; Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Melanie Bewerunge-HudlerMicroarray Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Alexander BrobeilInstitute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Matthias KloorInstitute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Hendrik BläkerInstitute of Pathology, University of Leipzig Medical Center, Leipzig, Germany.
Hermann BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Michael HoffmeisterDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: m.hoffmeister@dkfz.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDNA methylation biomarkers in colorectal cancer (CRC) tissue hold potential as prognostic indicators. However, individual studies have yielded heterogeneous results, and external validation is largely absent. We conducted a comprehensive external validation and meta-analysis of previously suggested gene methylation biomarkers for CRC prognosis.

methodsWe performed a systematic search to identify relevant studies investigating gene methylation biomarkers for CRC prognosis until March 2024. Our external validation cohort with long-term follow-up included 2303 patients with CRC from 22 hospitals in southwest Germany. We used Cox regression analyses to assess associations between previously suggested gene methylation biomarkers and prognosis, adjusting for clinical variables. We calculated pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) using random-effects models.

findingsOf 151 single gene and 29 multiple gene methylation biomarkers identified from 121 studies, 37 single gene and seven multiple gene biomarkers were significantly associated with CRC prognosis after adjustment for clinical variables. Moreover, the directions of these associations with prognosis remained consistent between the original studies and our validation analyses. Seven single biomarkers and two multi-biomarker signatures were significantly associated with CRC prognosis in the meta-analysis, with a relatively strong level of evidence for CDKN2A, WNT5A, MLH1, and EVL.

interpretationIn a comprehensive evaluation of the so far identified gene methylation biomarkers for CRC prognosis, we identified candidates with potential clinical relevance for further investigation.

fundingThe German Research Council, the Interdisciplinary Research Program of the National Center for Tumor Diseases (NCT), Germany, the German Federal Ministry of Education and Research.

Indexed as

Biomarkers, TumorColorectal NeoplasmsDNA MethylationFemaleGene Expression Regulation, NeoplasticHumansMalePrognosisProportional Hazards ModelsReproducibility of ResultsBiomarkers, TumorColorectal cancerExternal validationGene methylation biomarkersMeta-analysisPrognosis

Identifiers

PMID38917511
PMCPMC11255517

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.