title: A Molecular Model for Predicting Overall Survival in Patients with Metastatic Clear Cell Renal Carcinoma: Results from CALGB 90206 (Alliance).
abstract: BACKGROUND
  Prognosis associated with metastatic renal cell carcinoma (mRCC) can vary widely.
  
  
  METHODS
  This study used pretreatment nephrectomy specimens from a randomized phase III trial. Expression levels of candidate genes were determined from archival tumors using the OpenArray® platform for TaqMan® RT-qPCR. The dataset was randomly divided at 2:1 ratio into training (n = 221) and testing (n = 103) sets to develop a multigene prognostic signature.
  
  
  RESULTS
  Gene expressions were measured in 324 patients. In the training set, multiple models testing 424 candidate genes identified a prognostic signature containing 8 genes plus MSKCC clinical risk factors. In the testing set, the time dependent (td) AUC for a prognostic model containing the 8 genes with and without MSKCC risk factors were 0.72 and 0.69, respectively. The tdAUC for the clinical risk factors alone was 0.61. Additional primary mRCCs from patients with mRCC (n = 12) were sampled in multiple sites and standard deviations of gene expressions within a tumor were used as a measure of heterogeneity. All 8 genes in the final prognostic model met our criteria for minimal heterogeneity.
  
  
  CONCLUSIONS
  A molecular prognostic signature based on 8 genes was developed and is ready for external validation in this patient population and other related settings such as nonmetastatic RCC.
authors: Cedars-Sinai Medical Center, Los Angeles, CA, United States.
authors: Hyung L
authors: HL
authors: Kim
authors: Department of Biostatistics and Bioinformatics, and Alliance Statistics and Data Center, Duke University, Durham, NC, United States.
authors: Susan
authors: S
authors: Halabi
authors: Cedars-Sinai Medical Center, Los Angeles, CA, United States.
authors: Ping
authors: P
authors: Li
authors: GeneCentric Diagnostics, Durham, NC, United States.
authors: Greg
authors: G
authors: Mayhew
authors: University of California at San Francisco, San Francisco, CA, United States.
authors: Jeff
authors: J
authors: Simko
authors: GeneCentric Diagnostics, Durham, NC, United States.
authors: Andrew B
authors: AB
authors: Nixon
authors: University of California at San Francisco, San Francisco, CA, United States.
authors: Eric J
authors: EJ
authors: Small
authors: Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, United States.
authors: Brian
authors: B
authors: Rini
authors: Memorial Sloan Kettering Cancer Center, New York, NY, United States.
authors: Michael J
authors: MJ
authors: Morris
authors: Dana-Farber Cancer Institute, Boston, MA, United States.
authors: Mary-Ellen
authors: ME
authors: Taplin
authors: Department of Biostatistics and Bioinformatics, and Alliance Statistics and Data Center, Duke University, Durham, NC, United States.
authors: Daniel
authors: D
authors: George
mesh_terms: D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor; D002170:Canada; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D015233:Models, Statistical; D009362:Neoplasm Metastasis; D011379:Prognosis; D012307:Risk Factors; D014481:United States
chemical_list: D014408:Biomarkers, Tumor
keywords: Expression profile; Prognostic markers; Prognostic signature; Renal cell carcinoma