NDLI: DNA methylation associates with survival in non-metastatic clear cell renal cell carcinoma

Content Provider	Springer Nature : BioMed Central
Author	Evelönn, Emma Andersson Landfors, Mattias Haider, Zahra Köhn, Linda Ljungberg, Börje Roos, Göran Degerman, Sofie
Abstract	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 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 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 (pCSS5yr) p < 0.001 and cumulative incidence of progress (pCIP5yr) p < 0.001. An integrated genomic and epigenomic analysis in the ccRCCs, revealed significant correlations between the total number of genetic aberrations and total number of hypermethylated CpGs (R = 0.435, p < 0.001), and predicted mitotic age (R = 0.407, p < 0.001). We identified a promoter methylation classifier (PMC) panel consisting of 172 differently methylated CpGs accompanying progress of disease. Classifying non-metastatic patients using the PMC panel showed that PMC high tumors had a worse prognosis compared with the PMC low tumors (pCIP5yr 38% vs. 8%, p = 0.001), which was confirmed in non-metastatic ccRCCs in the publically available TCGA-KIRC dataset (pCIP5yr 39% vs. 16%, p < 0.001). Conclusion DNA methylation analysis at diagnosis in ccRCC has the potential to improve outcome-prediction in non-metastatic patients at diagnosis.
Related Links	https://bmccancer.biomedcentral.com/counter/pdf/10.1186/s12885-019-5291-3.pdf
Ending Page	16
Page Count	16
Starting Page	1
File Format	HTM / HTML
ISSN	14712407
DOI	10.1186/s12885-019-5291-3
Journal	BMC Cancer
Issue Number	1
Volume Number	19
Language	English
Publisher	BioMed Central
Publisher Date	2019-01-14
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Surgical Oncology Health Promotion and Disease Prevention Biomedicine Medicine Public Health Clear cell renal cell carcinoma DNA methylation Prognosis Genetic Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology Genetics
Journal Impact Factor	3.4/2023
5-Year Journal Impact Factor	3.8/2023

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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