Influence of gene expression on survival of clear cell renal cell carcinoma

Anders Berglund, Ernest K. Amankwah, Young Chul Kim, Philippe E. Spiess, Wade J. Sexton, Brandon Manley, Hyun Y. Park, Liang Wang, Jad Chahoud, Ratna Chakrabarti, Chang D. Yeo, Hung N. Luu, Giuliano D. Pietro, Alexander Parker, Jong Y. Park

Research output: Contribution to journalArticlepeer-review

Abstract

Approximately 10%-20% of patients with clinically localized clear cell renal cell carcinoma (ccRCC) at time of surgery will subsequently experience metastatic progression. Although considerable progression was seen in the systemic treatment of metastatic ccRCC in last 20 years, once ccRCC spreads beyond the confines of the kidney, 5-year survival is less than 10%. Therefore, significant clinical advances are urgently needed to improve overall survival and patient care to manage the growing number of patients with localized ccRCC. We comprehensively evaluated expression of 388 candidate genes related with survival of ccRCC by using TCGA RNAseq (n = 515), Total Cancer Care (TCC) expression array data (n = 298), and a well characterized Moffitt RCC cohort (n = 248). We initially evaluated all 388 genes for association with overall survival using TCGA and TCC data. Eighty-one genes were selected for further analysis and tested on Moffitt RCC cohort using NanoString expression analysis. Expression of nine genes (AURKA, AURKB, BIRC5, CCNE1, MK167, MMP9, PLOD2, SAA1, and TOP2A) was validated as being associated with poor survival. Survival prognostic models showed that expression of the nine genes and clinical factors predicted the survival in ccRCC patients with AUC value: 0.776, 0.821 and 0.873 for TCGA, TCC and Moffitt data set, respectively. Some of these genes have not been previously implicated in ccRCC survival and thus potentially offer insight into novel therapeutic targets. Future studies are warranted to validate these identified genes, determine their biological mechanisms and evaluate their therapeutic potential in preclinical studies.

Original languageEnglish (US)
Pages (from-to)8662-8675
Number of pages14
JournalCancer medicine
Volume9
Issue number22
DOIs
StatePublished - Nov 2020

Keywords

  • biomarkers
  • clear cell renal cell carcinoma
  • gene expression
  • survival

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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