In silico DNA methylation analysis identifies potential prognostic biomarkers in type 2 papillary renal cell carcinoma.

Autor:	Yang M; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota.; Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China., Hlady RA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota., Zhou D; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota., Ho TH; Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, Arizona., Robertson KD; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota.
Jazyk:	angličtina
Zdroj:	Cancer medicine [Cancer Med] 2019 Sep; Vol. 8 (12), pp. 5760-5768. Date of Electronic Publication: 2019 Jul 30.
DOI:	10.1002/cam4.2402
Abstrakt:	There are currently no effective treatments for advanced-stage papillary renal cell carcinoma (PRCC). The goal of this study is to define potential DNA methylation-based markers and treatment targets for advanced-stage type 2 PRCC. Progressive DNA methylation changes and copy number variation (CNV) from localized to advanced-stage type 2 PRCC are analyzed by using methylation data generated by TCGA's kidney renal papillary cell carcinoma (TCGA-KIRP, 450k array) project. Survival analyses are performed for the identified biomarkers and genes with CNV. In addition, expression of the corresponding genes is investigated by RNA-seq analysis. Progressive methylation changes in several CpGs from localized to advanced-stage type 2 PRCC are observed. Four CpGs (cg00489401, cg27649239, cg20555674, and cg07196505) in particular are identified as markers for differentiating between localized and advanced-stage type 2 PRCC. Copy number analysis reveals that copy gain of PTK7 mostly occurs in advanced-stage type 2 PRCC. Both the four CpG methylation changes and PTK7 copy number gain are associated with patient survival. RNA-seq analysis demonstrates that PTK7 copy gain leads to higher PTK7 expression relative to tumors without copy number gain. Moreover, PTK7 is significantly upregulated from localized to advanced-stage type 2 PRCC and is linked to cancer cell invasion. In conclusion, DNA methylation markers that differentiate between localized and advanced-stage type 2 PRCC may serve as useful markers for disease staging or outcome, while PTK7 copy gain represents a potential treatment target for advanced-stage type 2 PRCC. Stepwise methylation changes and copy number gain also associate with disease stage in PRCC patients. (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
Databáze:	MEDLINE
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