Evidence map›Paper›PMID 24708595›Full record

ArticleBMC cancer2014

Circulating cell-free methylated DNA and lactate dehydrogenase release in colorectal cancer.

Alexander B Philipp, Dorothea Nagel, Petra Stieber, Rolf Lamerz, Isabel Thalhammer, Andreas Herbst, Frank T Kolligs

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 2 pooled it
3.1field-weighted citation impact, top 8% 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

36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 53 citations in OpenAlex.

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  16. Epigenetics of colorectal cancer: biomarker and therapeutic potential.Nature reviews. Gastroenterology & hepatology · 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

7 authors at 1 institution in 1 country.

Alexander B Philipp
Dorothea Nagel
Petra Stieber
Rolf Lamerz
Isabel Thalhammer
Andreas Herbst
Frank T KolligsDepartment of Medicine II, Ludwig-Maximilians-Universität München, Marchioninistr, 15, 81377 Munich, Germany. Frank.Kolligs@med.uni-muenchen.de.
Ludwig-Maximilians-Universität München · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHypermethylation of DNA is an epigenetic alteration commonly found in colorectal cancer (CRC) and can also be detected in blood samples of cancer patients. Methylation of the genes helicase-like transcription factor (HLTF) and hyperplastic polyposis 1 (HPP1) have been proposed as prognostic, and neurogenin 1 (NEUROG1) as diagnostic biomarker. However the underlying mechanisms leading to the release of these genes are unclear. This study aimed at examining the possible correlation of the presence of methylated genes NEUROG1, HLTF and HPP1 in serum with tissue breakdown as a possible mechanism using serum lactate dehydrogenase (LDH) as a surrogate marker. Additionally the prognostic impact of these markers was examined.

methodsPretherapeutic serum samples from 259 patients from all cancer stages were analyzed. Presence of hypermethylation of the genes HLTF, HPP1, and NEUROG1 was examined using methylation-specific quantitative PCR (MethyLight). LDH was determined using an UV kinetic test.

resultsHypermethylation of HLTF and HPP1 was detected significantly more often in patients with elevated LDH levels (32% vs. 12% [p = 0.0005], and 68% vs. 11% [p < 0.0001], respectively). Also, higher LDH values correlated with a higher percentage of a fully methylated reference in a linear fashion (Spearman correlation coefficient 0.18 for HLTF [p = 0.004]; 0.49 [p < .0001] for HPP1). No correlation between methylation of NEUROG1 and LDH was found in this study. Concerning the clinical characteristics, high levels of LDH as well as methylation of HLTF and HPP1 were significantly associated with larger and more advanced stages of CRC. Accordingly, these three markers were correlated with significantly shorter survival in the overall population. Moreover, all three identified patients with a worse prognosis in the subgroup of stage IV patients.

conclusionsWe were able to provide evidence that methylation of HLTF and especially HPP1 detected in serum is strongly correlated with cell death in CRC using LDH as surrogate marker. Additionally, we found that prognostic information is given by both HLTF and HPP1 as well as LDH. In sum, determining the methylation of HLTF and HPP1 in serum might be useful in order to identify patients with more aggressive tumors.

Indexed as

AgedAged, 80 and overBasic Helix-Loop-Helix ProteinsBiomarkers, TumorColorectal NeoplasmsDNA-Binding ProteinsDNA MethylationFemaleHumansL-Lactate DehydrogenaseMaleMembrane ProteinsNeoplasm ProteinsNeoplasm StagingNeoplastic Cells, CirculatingNerve Tissue ProteinsBasic Helix-Loop-Helix ProteinsBiomarkers, TumorDNA-Binding ProteinsHLTF protein, humanL-Lactate DehydrogenaseMembrane ProteinsNeoplasm ProteinsNerve Tissue ProteinsNEUROG1 protein, humanTMEFF2 protein, humanTranscription Factors

Identifiers

PMID24708595
PMCPMC4021086
OpenAlexW1973385340

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.