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

作者：Kim Hyung L^*; Halabi Susan; Li Ping; Mayhew Greg; Simko Jeff; Nixon Andrew B; Small Eric J; Rini Brian; Morris Michael J; Taplin Mary Ellen; George Daniel

来源：EBioMedicine, 2015, 2(11): 1814-1820.

DOI：10.1016/j.ebiom.2015.09.012

• Renal cell carcinoma
• Prognostic markers
• Prognostic signature
• Expression profile

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 (R) platform for TaqMan (R) 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.

• 出版日期2015-11