DNA methylation associates with survival in non-metastatic clear cell renal cell carcinoma.
Aged
Biomarkers, Tumor
Carcinoma, Renal Cell
/ genetics
Computational Biology
/ methods
CpG Islands
DNA Methylation
Disease Progression
Epigenesis, Genetic
Female
Gene Expression Regulation, Neoplastic
Genetic Variation
Humans
Kidney Neoplasms
/ genetics
Male
Middle Aged
Neoplasm Grading
Neoplasm Metastasis
Neoplasm Staging
Prognosis
Promoter Regions, Genetic
ROC Curve
Clear cell renal cell carcinoma
DNA methylation
Genetic
Prognosis
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
14 Jan 2019
14 Jan 2019
Historique:
received:
25
09
2018
accepted:
07
01
2019
entrez:
16
1
2019
pubmed:
16
1
2019
medline:
24
4
2019
Statut:
epublish
Résumé
Clear cell renal cell carcinoma (ccRCC) is the most common subtype among renal cancer and is associated with poor prognosis if metastasized. Up to one third of patients with local disease at diagnosis will develop metastasis after nephrectomy, and there is a need for new molecular markers to identify patients with high risk of tumor progression. In the present study, we performed genome-wide promoter DNA methylation analysis at diagnosis to identify DNA methylation profiles associated with risk for progress. Diagnostic tissue samples from 115 ccRCC patients were analysed by Illumina HumanMethylation450K arrays and methylation status of 155,931 promoter associated CpGs were related to genetic aberrations, gene expression and clinicopathological parameters. The ccRCC samples separated into two clusters (cluster A/B) based on genome-wide promoter methylation status. The samples in these clusters differed in tumor diameter (p < 0.001), TNM stage (p < 0.001), morphological grade (p < 0.001), and patients outcome (5 year cancer specific survival (pCSS DNA methylation analysis at diagnosis in ccRCC has the potential to improve outcome-prediction in non-metastatic patients at diagnosis.
Sections du résumé
BACKGROUND
BACKGROUND
Clear cell renal cell carcinoma (ccRCC) is the most common subtype among renal cancer and is associated with poor prognosis if metastasized. Up to one third of patients with local disease at diagnosis will develop metastasis after nephrectomy, and there is a need for new molecular markers to identify patients with high risk of tumor progression. In the present study, we performed genome-wide promoter DNA methylation analysis at diagnosis to identify DNA methylation profiles associated with risk for progress.
METHOD
METHODS
Diagnostic tissue samples from 115 ccRCC patients were analysed by Illumina HumanMethylation450K arrays and methylation status of 155,931 promoter associated CpGs were related to genetic aberrations, gene expression and clinicopathological parameters.
RESULTS
RESULTS
The ccRCC samples separated into two clusters (cluster A/B) based on genome-wide promoter methylation status. The samples in these clusters differed in tumor diameter (p < 0.001), TNM stage (p < 0.001), morphological grade (p < 0.001), and patients outcome (5 year cancer specific survival (pCSS
CONCLUSION
CONCLUSIONS
DNA methylation analysis at diagnosis in ccRCC has the potential to improve outcome-prediction in non-metastatic patients at diagnosis.
Identifiants
pubmed: 30642274
doi: 10.1186/s12885-019-5291-3
pii: 10.1186/s12885-019-5291-3
pmc: PMC6332661
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
65Subventions
Organisme : Lion's Cancer Research Foundation, Umeå
ID : LPK
Organisme : Kempestiftelserna
ID : nr
Organisme : Västerbotten Läns Landsting
ID : nr
Organisme : Uppsala-Umeå Comprehensive Cancer Consortium
ID : nr
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