title: Characterization of clear cell renal cell carcinoma by gene expression profiling.
abstract: OBJECTIVE
  Use global gene expression to characterize differences between high-grade and low-grade clear cell renal cell carcinoma (ccRCC) compared with normal and benign renal tissue.
  
  
  METHODS
  Tissue samples were collected from patients undergoing surgical resection for ccRCC. Affymetrix gene expression arrays were used to examine global gene expression patterns in high- (n = 16) and low-grade ccRCC (n = 13) as well as in samples from normal kidney (n =14) and benign kidney disease (n = 6). Differential gene expression was determined by analysis of variance with a false discovery rate of 1% and a 2-fold cutoff.
  
  
  RESULTS
  Comparing high-grade ccRCC with each of normal and benign kidney resulted in 1,833 and 2,208 differentially expressed genes, respectively. Of these, 930 were differentially expressed in both comparisons. In order to identify genes most related to progression of ccRCC, these differentially expressed genes were filtered to identify genes that showed a pattern of expression with a magnitude of change greater in high-grade ccRCC in the comparison to low-grade ccRCC. This resulted in the identification of genes such as TMEM45A, ceruloplasmin, and E-cadherin that were involved in cell processes of cell differentiation and response to hypoxia. Additionally changes in HIF1α and TNF signaling are highly represented by changes between high- and low-grade ccRCC.
  
  
  CONCLUSIONS
  Gene expression differences between high-grade and low-grade ccRCC may prove to be valuable biomarkers for advanced ccRCC. In addition, altered signaling between grades of ccRCC may provide important insight into the biology driving the progression of ccRCC and potential targets for therapy.
authors.affiliation: Beaumont BioBank, Beaumont Health System, Royal Oak, MI. Electronic address: Bryan.Thibodeau@beaumont.edu.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Thibodeau
authors.affiliation: Department of Urology, Beaumont Health System, Royal Oak, MI.
authors.forename: Matthew
authors.initials: M
authors.lastname: Fulton
authors.affiliation: Beaumont BioBank, Beaumont Health System, Royal Oak, MI.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Fortier
authors.affiliation: Beaumont BioBank, Beaumont Health System, Royal Oak, MI.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Geddes
authors.affiliation: Beaumont BioBank, Beaumont Health System, Royal Oak, MI.
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Pruetz
authors.affiliation: Beaumont BioBank, Beaumont Health System, Royal Oak, MI.
authors.forename: Samreen
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: Oakland University, Rochester, MI.
authors.forename: Amy
authors.initials: A
authors.lastname: Banes-Berceli
authors.affiliation: Department of Anatomic Pathology; Beaumont Health System, Royal Oak, MI.
authors.forename: Ping L
authors.initials: PL
authors.lastname: Zhang
authors.affiliation: Beaumont BioBank, Beaumont Health System, Royal Oak, MI.
authors.forename: George D
authors.initials: GD
authors.lastname: Wilson
authors.affiliation: Department of Urology, Beaumont Health System, Royal Oak, MI.
authors.forename: Jason
authors.initials: J
authors.lastname: Hafron
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D046888:Tissue Array Analysis; D055815:Young Adult
keywords: Clear cell renal cell carcinoma; Fuhrman grading; Gene expression; Microarray