A Molecular Model for Predicting Overall Survival in Patients with Metastatic Clear Cell Renal Carcinoma: Results from CALGB 90206 (Alliance).

Published online

Journal Article

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. FINDINGS: 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.

Full Text

Duke Authors

Cited Authors

  • Kim, HL; Halabi, S; Li, P; Mayhew, G; Simko, J; Nixon, AB; Small, EJ; Rini, B; Morris, MJ; Taplin, M-E; George, D; Alliance for Clinical Trials in Oncology,

Published Date

  • November 2015

Published In

Volume / Issue

  • 2 / 11

Start / End Page

  • 1814 - 1820

PubMed ID

  • 26870806

Pubmed Central ID

  • 26870806

Electronic International Standard Serial Number (EISSN)

  • 2352-3964

Digital Object Identifier (DOI)

  • 10.1016/j.ebiom.2015.09.012

Language

  • eng

Conference Location

  • Netherlands