Faculty Collaboration Database

Influence of gene expression on survival of clear cell renal cell carcinoma. Cancer Med 2020 Nov;9(22):8662-8675

Date

09/29/2020

Pubmed ID

32986937

Pubmed Central ID

PMC7666730

DOI

10.1002/cam4.3475

Scopus ID

2-s2.0-85091605376 (requires institutional sign-in at Scopus site)   11 Citations

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.

Author List

Berglund A, Amankwah EK, Kim YC, Spiess PE, Sexton WJ, Manley B, Park HY, Wang L, Chahoud J, Chakrabarti R, Yeo CD, Luu HN, Pietro GD, Parker A, Park JY

Author

Ernest Amankwah PhD Director, Associate Professor in the Clinical and Translational Science Institute department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Biomarkers, Tumor
Carcinoma, Renal Cell
Databases, Nucleic Acid
Epigenesis, Genetic
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Kidney Neoplasms
Male
Predictive Value of Tests
Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase
Prognosis
Risk Assessment
Risk Factors
Serum Amyloid A Protein
Transcriptome