Differences in Prostate Cancer Transcriptomes by Age at Diagnosis: Are Primary Tumors from Older Men Inherently Different?
Journal
Cancer prevention research (Philadelphia, Pa.)
ISSN: 1940-6215
Titre abrégé: Cancer Prev Res (Phila)
Pays: United States
ID NLM: 101479409
Informations de publication
Date de publication:
01 12 2022
01 12 2022
Historique:
received:
03
05
2022
revised:
03
08
2022
accepted:
01
09
2022
pubmed:
21
9
2022
medline:
3
12
2022
entrez:
20
9
2022
Statut:
ppublish
Résumé
Older age at diagnosis is consistently associated with worse clinical outcomes in prostate cancer. We sought to characterize gene expression profiles of prostate tumor tissue by age at diagnosis. We conducted a discovery analysis in The Cancer Genome Atlas prostate cancer dataset (n = 320; 29% of men >65 years at diagnosis), using linear regressions of age at diagnosis and mRNA expression and adjusting for TMPRSS2:ERG fusion status and race. This analysis identified 13 age-related candidate genes at FDR < 0.1, six of which were also found in an analysis additionally adjusted for Gleason score. We then validated the 13 age-related genes in a transcriptome study nested in the Health Professionals Follow-up Study and Physicians' Health Study (n = 374; 53% of men >65 years). Gene expression differences by age in the 13 candidate genes were directionally consistent, and age at diagnosis was weakly associated with the 13-gene score. However, the age-related genes were not consistently associated with risk of metastases and prostate cancer-specific death. Collectively, these findings argue against tumor genomic differences as a main explanation for age-related differences in prostate cancer prognosis. Older age at diagnosis is consistently associated with worse clinical outcomes in prostate cancer. This study with independent discovery and validation sets and long-term follow-up suggests that prevention of lethal prostate cancer should focus on implementing appropriate screening, staging, and treatment among older men without expecting fundamentally different tumor biology.
Identifiants
pubmed: 36125434
pii: 709260
doi: 10.1158/1940-6207.CAPR-22-0212
pmc: PMC9722523
mid: NIHMS1835584
doi:
Substances chimiques
Oncogene Proteins, Fusion
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
815-825Subventions
Organisme : NCI NIH HHS
ID : P50 CA090381
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA227190
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA167552
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA136578
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA006516
Pays : United States
Informations de copyright
©2022 American Association for Cancer Research.
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