A comparative study of PCS and PAM50 prostate cancer classification schemes.
Journal
Prostate cancer and prostatic diseases
ISSN: 1476-5608
Titre abrégé: Prostate Cancer Prostatic Dis
Pays: England
ID NLM: 9815755
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
25
05
2020
accepted:
15
01
2021
revised:
20
12
2020
pubmed:
4
2
2021
medline:
2
2
2022
entrez:
3
2
2021
Statut:
ppublish
Résumé
Two prostate cancer (PC) classification methods based on transcriptome profiles, a de novo method referred to as the "Prostate Cancer Classification System" (PCS) and a variation of the established PAM50 breast cancer algorithm, were recently proposed. Both studies concluded that most human PC can be assigned to one of three tumor subtypes, two categorized as luminal and one as basal, suggesting the two methods reflect consistency in underlying biology. Despite the similarity, differences and commonalities between the two classification methods have not yet been reported. Here, we describe a comparison of the PCS and PAM50 classification systems. PCS and PAM50 signatures consisting of 37 (PCS37) and 50 genes, respectively, were used to categorize 9,947 PC patients into PCS and PAM50 classes. Enrichment of hallmark gene sets and luminal and basal marker gene expression were assessed in the same datasets. Finally, survival analysis was performed to compare PCS and PAM50 subtypes in terms of clinical outcomes. PCS and PAM50 subtypes show clear differential expression of PCS37 and PAM50 genes. While only three genes are shared in common between the two systems, there is some consensus between three subtype pairs (PCS1 versus Luminal B, PCS2 versus Luminal A, and PCS3 versus Basal) with respect to gene expression, cellular processes, and clinical outcomes. PCS categories displayed better separation of cellular processes and luminal and basal marker gene expression compared to PAM50. Although both PCS1 and Luminal B tumors exhibited the worst clinical outcomes, outcomes between aggressive and less aggressive subtypes were better defined in the PCS system, based on larger hazard ratios observed. The PCS and PAM50 classification systems are similar in terms of molecular profiles and clinical outcomes. However, the PCS system exhibits greater separation in multiple clinical outcomes and provides better separation of prostate luminal and basal characteristics.
Sections du résumé
BACKGROUND
Two prostate cancer (PC) classification methods based on transcriptome profiles, a de novo method referred to as the "Prostate Cancer Classification System" (PCS) and a variation of the established PAM50 breast cancer algorithm, were recently proposed. Both studies concluded that most human PC can be assigned to one of three tumor subtypes, two categorized as luminal and one as basal, suggesting the two methods reflect consistency in underlying biology. Despite the similarity, differences and commonalities between the two classification methods have not yet been reported.
METHODS
Here, we describe a comparison of the PCS and PAM50 classification systems. PCS and PAM50 signatures consisting of 37 (PCS37) and 50 genes, respectively, were used to categorize 9,947 PC patients into PCS and PAM50 classes. Enrichment of hallmark gene sets and luminal and basal marker gene expression were assessed in the same datasets. Finally, survival analysis was performed to compare PCS and PAM50 subtypes in terms of clinical outcomes.
RESULTS
PCS and PAM50 subtypes show clear differential expression of PCS37 and PAM50 genes. While only three genes are shared in common between the two systems, there is some consensus between three subtype pairs (PCS1 versus Luminal B, PCS2 versus Luminal A, and PCS3 versus Basal) with respect to gene expression, cellular processes, and clinical outcomes. PCS categories displayed better separation of cellular processes and luminal and basal marker gene expression compared to PAM50. Although both PCS1 and Luminal B tumors exhibited the worst clinical outcomes, outcomes between aggressive and less aggressive subtypes were better defined in the PCS system, based on larger hazard ratios observed.
CONCLUSION
The PCS and PAM50 classification systems are similar in terms of molecular profiles and clinical outcomes. However, the PCS system exhibits greater separation in multiple clinical outcomes and provides better separation of prostate luminal and basal characteristics.
Identifiants
pubmed: 33531653
doi: 10.1038/s41391-021-00325-4
pii: 10.1038/s41391-021-00325-4
pmc: PMC8326303
mid: NIHMS1684231
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
733-742Subventions
Organisme : NCI NIH HHS
ID : P01 CA098912
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA198900
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA220327
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA218356
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA233452
Pays : United States
Informations de copyright
© 2021. The Author(s).
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