title: High risk of development of renal cell tumor in end-stage kidney disease: the role of microenvironment.
abstract: 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.
authors.affiliation: Medical Faculty, University of Pecs, Pecs, Hungary.
authors.forename: Anetta
authors.initials: A
authors.lastname: Nagy
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Walter
authors.affiliation: Department of Genetic Identification, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Zubakov
authors.affiliation: Medical Faculty, University of Pecs, Pecs, Hungary. G.Kovacs@gmx.de.|Medical Faculty, University of Heidelberg, Heidelberg, Germany. G.Kovacs@gmx.de.
authors.forename: Gyula
authors.initials: G
authors.lastname: Kovacs
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000473:pathology*; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D016209:Interleukin-8 / Q000235:genetics; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000473:pathology*; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D023063:Receptors, Interleukin-8B / Q000235:genetics; D012306:Risk; D013234:Stem Cells / Q000473:pathology; D059016:Tumor Microenvironment / Q000235:genetics*
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D023063:Receptors, Interleukin-8B
keywords: CXCL8; CXCR2; End-stage kidney disease; Gene expression signature; Inflammatory microenvironment; SCEL; Tumor development