Evidence map›Paper›PMID 23965899›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013

Promoter CpG island methylation of genes in key cancer pathways associates with clinical outcome in high-grade serous ovarian cancer.

Wei Dai, Constanze Zeller, Nahal Masrour, Nadeem Siddiqui, James Paul, Robert Brown

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 2 pooled it
2.8field-weighted citation impact, top 9% 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

31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.

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  14. [Overexpression of histone deacetylase 11 suppresses basal-like breast cancer cell invasion and metastasis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2019
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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

6 authors at 3 institutions in 1 country.

Wei Dai *Epigenetics Unit, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London, UK W12 0NN.
Constanze Zeller *Epigenetics Unit, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London, UK W12 0NN.
Nahal MasrourEpigenetics Unit, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London, UK W12 0NN.
Nadeem SiddiquiDepartment of Gynaecology, Glasgow Royal Infirmary, Glasgow, UK G31 2ER.
James PaulCancer Research UK Clinical Trials Unit, Glasgow University, The Beatson West of Scotland Cancer Centre, Level 0, 1053 Gt. Western Road, Glasgow, UK G12 0YN.
Robert BrownEpigenetics Unit, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London, UK W12 0NN.
Institute of Cancer Research · GBImperial College London · GBCancer Research UK Clinical Trials Unit · GB

Funding

Cancer Research UK 13086Cancer Research UK 15960Cancer Research UK A13086Cancer Research UK C536/A13086
6 · The paper itself

Abstract

purposeWe aimed to identify DNA methylation biomarkers of progression-free survival (PFS) to platinum-based chemotherapy in high-grade serous ovarian cancer (HGSOC) within biologically relevant ovarian cancer-associated pathways. EXPERIMENTAL

designAssociation with PFS of CpG island (CGI) promoter DNA methylation at genes in the pathways Akt/mTOR, p53, redox, and homologous recombination DNA repair was sought with PFS as the primary objective in a prospectively collected ovarian cancer cohort (n = 150). Significant loci were validated for associations between PFS, methylation, and gene expression in an independent The Cancer Genome Atlas (TCGA) data set of HGSOC (n = 311).

resultsDNA methylation at 29 CGI loci linked to 28 genes was significantly associated with PFS, independent from conventional clinical prognostic factors (adjusted P < 0.05). Of 17 out of the 28 genes represented in the TCGA data set, methylation of VEGFB, VEGFA, HDAC11, FANCA, E2F1, GPX4, PRDX2, RAD54L, and RECQL4 was prognostic in this independent patient cohort (one-sided P < 0.05, false discovery rate < 10%). A multivariate Cox model was constructed, with clinical parameters (age, stage, grade, and histologic type) and significant loci. The final model included NKD1, VEGFB, and PRDX2 as the three best predictors of PFS (P = 6.62 × 10(-6), permutation test P < 0.05). Focussing only on known VEGFs in the TCGA cohort showed that methylation at promoters of VEGFA, VEGFB, and VEGFC was significantly associated with PFS.

conclusionsA three loci model of DNA methylation could identify two distinct prognostic groups of patients with ovarian cancer (PFS: HR = 2.29, P = 3.34 × 10(-5); overall survival: HR = 1.87, P = 0.007) and patients more likely to have poor response to chemotherapy (OR = 3.45, P = 0.012).

Indexed as

CpG IslandsDNA MethylationPromoter Regions, GeneticAntineoplastic Combined Chemotherapy ProtocolsCystadenocarcinoma, SerousDisease ProgressionFemaleHumansNeoplasm GradingNeoplasm StagingOvarian NeoplasmsPlatinumPrognosisSignal TransductionTreatment OutcomeVascular Endothelial Growth Factor APlatinumVascular Endothelial Growth Factor A

Identifiers

PMID23965899
PMCPMC4913863
OpenAlexW2127840259

What OpenQuestion holds

Textmetadata
LicenceTDM
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.