ArticleBMC medical genomics2008
Discovery of DNA methylation markers in cervical cancer using relaxation ranking.
Article in BMC medical genomics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Epigenomic characterization of locally advanced anal cancer: a radiation therapy oncology group 98-11 specimen study.Diseases of the colon and rectum · 2014Trial
- DNA methylation markers as triage test for the early identification of cervical lesions in a Chinese population.International journal of cancer · 2021Article
- A distinct concerted mechanism of structural dynamism defines activity of human serine protease HtrA3.The Biochemical journal · 2020Article
- As a downstream target of the AKT pathway, NPTX1 inhibits proliferation and promotes apoptosis in hepatocellular carcinoma.Bioscience reports · 2019Article
- DNA methylation markers as a triage test for identification of cervical lesions in a high risk human papillomavirus positive screening cohort.International journal of cancer · 2019Article
- NPTX1 promotes metastasis via integrin/FAK signaling in gastric cancer.Cancer management and research · 2019Article
- Recent Advances on the Molecular Mechanism of Cervical Carcinogenesis Based on Systems Biology Technologies.Computational and structural biotechnology journal · 2019Review
- Incorporating EBO-HSIC with SVM for Gene Selection Associated with Cervical Cancer Classification.Journal of medical systems · 2018Article
- Article
- Identification of methylation markers for the prediction of nodal metastasis in oral and oropharyngeal squamous cell carcinoma.Epigenetics · 2015Article
- Functional validation of putative tumor suppressor gene C13ORF18 in cervical cancer by Artificial Transcription Factors.Molecular oncology · 2013Article
- Genome-wide promoter methylation analysis in neuroblastoma identifies prognostic methylation biomarkers.Genome biology · 2012Article
- DNA hypermethylation biomarkers to predict response to cisplatin treatment, radiotherapy or chemoradiation: the present state of art.Cellular oncology (Dordrecht, Netherlands) · 2012Review
- Genome-wide CpG island methylation analysis implicates novel genes in the pathogenesis of renal cell carcinoma.Epigenetics · 2012Article
- Effects of DNMT1 silencing on malignant phenotype and methylated gene expression in cervical cancer cells.Journal of experimental & clinical cancer research : CR · 2011Article
- MiR-185 targets the DNA methyltransferases 1 and regulates global DNA methylation in human glioma.Molecular cancer · 2011Article
- Novel candidate colorectal cancer biomarkers identified by methylation microarray-based scanning.Endocrine-related cancer · 2011Article
- What will it take to obtain DNA methylation markers for early cervical cancer detection?Gynecologic oncology · 2009Article
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTo discover cancer specific DNA methylation markers, large-scale screening methods are widely used. The pharmacological unmasking expression microarray approach is an elegant method to enrich for genes that are silenced and re-expressed during functional reversal of DNA methylation upon treatment with demethylation agents. However, such experiments are performed in in vitro (cancer) cell lines, mostly with poor relevance when extrapolating to primary cancers. To overcome this problem, we incorporated data from primary cancer samples in the experimental design. A strategy to combine and rank data from these different data sources is essential to minimize the experimental work in the validation steps.
aimTo apply a new relaxation ranking algorithm to enrich DNA methylation markers in cervical cancer.
resultsThe application of a new sorting methodology allowed us to sort high-throughput microarray data from both cervical cancer cell lines and primary cervical cancer samples. The performance of the sorting was analyzed in silico. Pathway and gene ontology analysis was performed on the top-selection and gives a strong indication that the ranking methodology is able to enrich towards genes that might be methylated. Terms like regulation of progression through cell cycle, positive regulation of programmed cell death as well as organ development and embryonic development are overrepresented. Combined with the highly enriched number of imprinted and X-chromosome located genes, and increased prevalence of known methylation markers selected from cervical (the highest-ranking known gene is CCNA1) as well as from other cancer types, the use of the ranking algorithm seems to be powerful in enriching towards methylated genes.Verification of the DNA methylation state of the 10 highest-ranking genes revealed that 7/9 (78%) gene promoters showed DNA methylation in cervical carcinomas. Of these 7 genes, 3 (SST, HTRA3 and NPTX1) are not methylated in normal cervix tissue.
conclusionThe application of this new relaxation ranking methodology allowed us to significantly enrich towards methylation genes in cancer. This enrichment is both shown in silico and by experimental validation, and revealed novel methylation markers as proof-of-concept that might be useful in early cancer detection in cervical scrapings.
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