High risk of development of renal cell tumor in end-stage kidney disease: the role of microenvironment
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End-stage renal disease (ESRD) and acquired cystic renal disease (ACRD) are associated with high risk of development of renal cell tumors (RCT) displaying unusual phenotype and genotype. The underlying molecular mechanism is not yet known. To explore the molecular microenvironment, we have established the expression profile of ESRD/ACRD kidneys. RNA extracted from normal and ESRD/ACRD kidneys and distinct types of RCT was subjected to Affymetrix HG U133 micro array analysis. A gene expression signature indicated cancer-related biological processes in the remodeling of ESRD/ACRD kidneys. Quantitative RT-PCR studies confirmed a specific gene signature including a functional group of inflammatory cytokines and also cytokeratins associated with stem cell characteristics of epithelial cells. Several of the signature genes including the SCEL were expressed in ESRD/ACRD-associated papillary RCT as well. Immunohistological analysis confirmed the expression of CXCL8 and its receptor CXCR2 as well as the expression of SCEL in hyperplastic tubular, cystic, and papillary structures and RCTs in ESRD/ACRD kidney. Our data indicates that ESRD/ACRD is a novel disease and the inflammatory microenvironment altered plasticity, and stem cell characteristics of epithelial cells may be associated with the high risk of tumor development.
KeywordsEnd-stage kidney disease Gene expression signature Inflammatory microenvironment Tumor development CXCL8 CXCR2 SCEL
This work was supported by a grant of the Else-Kröner-Fresenius Stiftung, Homburg, Germany and in part by the Medical Faculty, University of Pécs, Hungary (PTE AOK KA2014/1). The authors express their appreciation to Drs. G. Staehler, B. Schulze-Brüggemann, D. Ferluga, and Mr. D. Cranston for making end-stage kidneys available and to B. Veszpremi for collecting fetal kidneys. The sciellin antibody (SC4) was kindly provided by Dr. H.P. Baden (Massachusetts General Hospital, Boston, USA).
AN and GK designed the study and wrote the manuscript. AN and DZ evaluated the array expression study. AN and EW carried out the RT-PCR analysis. AN and GK performed the immunohistochemistry.
Compliance with ethical standards
Conflicts of interest
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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