title: Role of inflammatory related gene expression in clear cell renal cell carcinoma development and clinical outcomes.
abstract: OBJECTIVE
  Renal cell carcinoma is the eighth most common cancer in the United States and clear cell renal carcinoma is the most common type. Many signaling pathways are implicated in clear cell renal carcinoma development, including the inflammation pathway. However, less is known about how gene expression variation in this pathway influences clear cell renal carcinoma development and clinical outcomes.
  
  
  METHODS
  Gene expression in tumor and adjacent normal tissues from 93 patients was detected using a genome-wide expression array. A panel of 661 inflammation related genes was then analyzed. Differential expression patterns between tumor and normal tissues were identified. Association with recurrence or survival was evaluated with genes showing significant association tested further in a validation set of 258 tumors using an independent platform (quantitative real-time polymerase chain reaction).
  
  
  RESULTS
  We identified 151 genes with at least a two-fold change in gene expression between adjacent normal tissue and tumor, of which most were up-regulated in tumors. A total of 20 genes significantly associated with recurrence and/or overall survival were selected for further validation. In the replication data set high expression of GADD45G was significantly associated with a 2.09-fold (95% CI 1.08-6.14, p = 0.034) increased risk of recurrence while high CARD9, NCF2 and CIITA expression was significantly associated with a 2.52-fold (95% CI 1.24-5.12, p = 0.010), 2.26-fold (95% CI 1.12-4.58, p = 0.023) and 2.11-fold (95% CI 1.05-4.27, p = 0.037) increased risk of death, respectively.
  
  
  CONCLUSIONS
  Results suggest that inflammation gene expression may be significant prognostic biomarkers for the risk of recurrence (GADD45G) and death (CARD9, CIITA and NCF2) in patients with clear cell renal carcinoma.
authors.affiliation: Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Tan
authors.forename: Michelle A T
authors.initials: MA
authors.lastname: Hildebrandt
authors.forename: Xia
authors.initials: X
authors.lastname: Pu
authors.forename: Maosheng
authors.initials: M
authors.lastname: Huang
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.forename: Surena F
authors.initials: SF
authors.lastname: Matin
authors.forename: Pheroze
authors.initials: P
authors.lastname: Tamboli
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Wood
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
mesh_terms: D000368:Aged; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005802:Genes, MHC Class II / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics; D000097642:GADD45 Proteins
chemical_list: D053468:CARD Signaling Adaptor Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019255:NADPH Oxidases; D009687:Nuclear Proteins; D015534:Trans-Activators; C505855:CARD9 protein, human; C485654:GADD45G protein, human; D000097642:GADD45 Proteins; C083728:MHC class II transactivator protein; C527764:NCF2 protein, human