Evidence map›Paper›PMID 29465788›Full record

Trial reportMolecular oncology2018

Biomarker potential of ST6GALNAC3 and ZNF660 promoter hypermethylation in prostate cancer tissue and liquid biopsies.

Christa Haldrup, Anne L Pedersen, Nadia Øgaard, Siri H Strand, Søren Høyer, Michael Borre, Torben F Ørntoft, Karina D Sørensen

Open access · goldAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Molecular oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
2.9field-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

40 citing papers in PubMed, 65 citations in OpenAlex.

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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 1 country.

Christa HaldrupDepartment of Molecular Medicine, Aarhus University Hospital, Denmark.
Anne L PedersenDepartment of Molecular Medicine, Aarhus University Hospital, Denmark.
Nadia ØgaardDepartment of Molecular Medicine, Aarhus University Hospital, Denmark.
Siri H StrandDepartment of Molecular Medicine, Aarhus University Hospital, Denmark.
Søren HøyerDepartment of Histopathology, Aarhus University Hospital, Denmark.
Michael BorreDepartment of Urology, Aarhus University Hospital, Denmark.
Torben F ØrntoftDepartment of Molecular Medicine, Aarhus University Hospital, Denmark.
Karina D SørensenDepartment of Molecular Medicine, Aarhus University Hospital, Denmark.
Aarhus University Hospital · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Current diagnostic and prognostic tools for prostate cancer (PC) are suboptimal, leading to overdiagnosis and overtreatment. Aberrant promoter hypermethylation of specific genes has been suggested as novel candidate biomarkers for PC that may improve diagnosis and prognosis. We here analyzed ST6GALNAC3 and ZNF660 promoter methylation in prostate tissues, and ST6GALNAC3, ZNF660, CCDC181, and HAPLN3 promoter methylation in liquid biopsies. First, using four independent patient sample sets, including a total of 110 nonmalignant (NM) and 705 PC tissue samples, analyzed by methylation-specific qPCR or methylation array, we found that hypermethylation of ST6GALNAC3 and ZNF660 was highly cancer-specific with areas under the curve (AUC) of receiver operating characteristic (ROC) curve analysis of 0.917-0.995 and 0.846-0.903, respectively. Furthermore, ZNF660 hypermethylation was significantly associated with biochemical recurrence in two radical prostatectomy (RP) cohorts of 158 and 392 patients and remained significant also in the subsets of patients with Gleason score ≤7 (univariate Cox regression and log-rank tests, P < 0.05), suggesting that ZNF660 methylation analysis can potentially help to stratify low-/intermediate-grade PCs into indolent vs. more aggressive subtypes. Notably, ZNF660 hypermethylation was also significantly associated with poor overall and PC-specific survival in the RP cohort (n = 158) with long clinical follow-up available. Moreover, as proof of principle, we successfully detected highly PC-specific hypermethylated circulating tumor DNA (ctDNA) for ST6GALNAC3, ZNF660, HAPLN3, and CCDC181 in liquid biopsies (serum) from 27 patients with PC vs. 10 patients with BPH, using droplet digital methylation-specific PCR analysis. Finally, we generated a three-gene (ST6GALNAC3/CCDC181/HAPLN3) ctDNA hypermethylation model, which detected PC with 100% specificity and 67% sensitivity. In conclusion, we here for the first time demonstrate diagnostic biomarker potential of ST6GALNAC3 and ZNF660 methylation, as well as prognostic biomarker potential of ZNF660. Furthermore, we show that hypermethylation of four genes can be detected in ctDNA in liquid biopsies (serum) from patients with PC.

Indexed as

DNA MethylationModels, BiologicalPromoter Regions, GeneticAgedAged, 80 and overBiomarkers, TumorDNA-Binding ProteinsHumansLiquid BiopsyMaleMiddle AgedNeoplasm ProteinsProstatic NeoplasmsSialyltransferasesBiomarkers, TumorDNA-Binding ProteinsNeoplasm ProteinsNeu5Ac N-acetylgalactosamine 2,6-sialyltransferaseSialyltransferasesbiomarkerepigeneticsliquid biopsyprostate cancerST6GALNAC3ZNF660

Identifiers

PMID29465788
PMCPMC5891052
OpenAlexW2793415408

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.