Age-related variations in gene expression patterns of renal cell carcinoma.
Aging
Cancer genomics
Cancer therapy
Gene expression analysis
Renal cell carcinoma
Journal
Urologic oncology
ISSN: 1873-2496
Titre abrégé: Urol Oncol
Pays: United States
ID NLM: 9805460
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
28
07
2018
revised:
29
10
2018
accepted:
05
11
2018
pubmed:
28
11
2018
medline:
4
9
2019
entrez:
28
11
2018
Statut:
ppublish
Résumé
Clear cell renal cell carcinoma (ccRCC) is known to occur across the adult lifetime traversing the spectrum of age-related organismal changes. Little is known as to how the aging process may affect the course of renal cell carcinoma (RCC) and the repertoire of genes involved. Using The Cancer Genome Atlas (n = 436) and Cancer Genomics of the Kidney (n = 89) datasets, we applied regression analysis to examine associations between patient age and gene expression profiles in ccRCC tumors and normal kidney tissues. Pathway enrichment analysis was performed to identify cellular process that is affected by aging in ccRCC. Moreover, connectivity mapping analysis was used to predict age-dependent response to drug treatments. Our analysis revealed different age-dependent gene expression spectra in ccRCC and normal kidney tissues. These findings were significant and independently reproducible in both datasets examined. Age up-regulated genes, showing higher expression in older patients, were significantly enriched (false discovery rate <0.05) in normal tissues for pathways associated with immune response and extracellular matrix organization, whereas age up-regulated genes in tumors were enriched for metabolism and oxidation pathways. Strikingly, age down-regulated genes in normal cells were also enriched for metabolism and oxidation, while those in tumors were enriched for extracellular matrix organization. Further in silico analysis of potential drug targets predicted preferential efficacy of Phosphoinositide 3-kinase inhibitor or immunotherapy in association with age. We report on previously unrecognized associations between age and molecular underpinnings of RCC, including age-associated expression of genes implicated in RCC development or treatment.
Sections du résumé
BACKGROUND
Clear cell renal cell carcinoma (ccRCC) is known to occur across the adult lifetime traversing the spectrum of age-related organismal changes. Little is known as to how the aging process may affect the course of renal cell carcinoma (RCC) and the repertoire of genes involved.
METHODS
Using The Cancer Genome Atlas (n = 436) and Cancer Genomics of the Kidney (n = 89) datasets, we applied regression analysis to examine associations between patient age and gene expression profiles in ccRCC tumors and normal kidney tissues. Pathway enrichment analysis was performed to identify cellular process that is affected by aging in ccRCC. Moreover, connectivity mapping analysis was used to predict age-dependent response to drug treatments.
RESULTS
Our analysis revealed different age-dependent gene expression spectra in ccRCC and normal kidney tissues. These findings were significant and independently reproducible in both datasets examined. Age up-regulated genes, showing higher expression in older patients, were significantly enriched (false discovery rate <0.05) in normal tissues for pathways associated with immune response and extracellular matrix organization, whereas age up-regulated genes in tumors were enriched for metabolism and oxidation pathways. Strikingly, age down-regulated genes in normal cells were also enriched for metabolism and oxidation, while those in tumors were enriched for extracellular matrix organization. Further in silico analysis of potential drug targets predicted preferential efficacy of Phosphoinositide 3-kinase inhibitor or immunotherapy in association with age.
CONCLUSION
We report on previously unrecognized associations between age and molecular underpinnings of RCC, including age-associated expression of genes implicated in RCC development or treatment.
Identifiants
pubmed: 30478010
pii: S1078-1439(18)30452-6
doi: 10.1016/j.urolonc.2018.11.006
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
166-175Informations de copyright
Copyright © 2018. Published by Elsevier Inc.