Pan-cancer analysis of genomic and transcriptomic data reveals the prognostic relevance of human proteasome genes in different cancer types.
Cancer
Gene expression profiling
Prognosis
Prognostic biomarkers
Proteasome gene family
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
19 Sep 2022
19 Sep 2022
Historique:
received:
14
01
2021
accepted:
05
09
2022
entrez:
19
9
2022
pubmed:
20
9
2022
medline:
23
9
2022
Statut:
epublish
Résumé
The human proteasome gene family (PSM) consists of 49 genes that play a crucial role in cancer proteostasis. However, little is known about the effect of PSM gene expression and genetic alterations on clinical outcome in different cancer forms. Here, we performed a comprehensive pan-cancer analysis of genetic alterations in PSM genes and the subsequent prognostic value of PSM expression using data from The Cancer Genome Atlas (TCGA) containing over 10,000 samples representing up to 33 different cancer types. External validation was performed using a breast cancer cohort and KM plotter with four cancer types. The PSM genetic alteration frequency was high in certain cancer types (e.g. 67%; esophageal adenocarcinoma), with DNA amplification being most common. Compared with normal tissue, most PSM genes were predominantly overexpressed in cancer. Survival analysis also established a relationship with PSM gene expression and adverse clinical outcome, where PSMA1 and PSMD11 expression were linked to more unfavorable prognosis in ≥ 30% of cancer types for both overall survival (OS) and relapse-free interval (PFI). Interestingly, PSMB5 gene expression was associated with OS (36%) and PFI (27%), and OS for PSMD2 (42%), especially when overexpressed. These findings indicate that several PSM genes may potentially be prognostic biomarkers and novel therapeutic targets for different cancer forms.
Sections du résumé
BACKGROUND
BACKGROUND
The human proteasome gene family (PSM) consists of 49 genes that play a crucial role in cancer proteostasis. However, little is known about the effect of PSM gene expression and genetic alterations on clinical outcome in different cancer forms.
METHODS
METHODS
Here, we performed a comprehensive pan-cancer analysis of genetic alterations in PSM genes and the subsequent prognostic value of PSM expression using data from The Cancer Genome Atlas (TCGA) containing over 10,000 samples representing up to 33 different cancer types. External validation was performed using a breast cancer cohort and KM plotter with four cancer types.
RESULTS
RESULTS
The PSM genetic alteration frequency was high in certain cancer types (e.g. 67%; esophageal adenocarcinoma), with DNA amplification being most common. Compared with normal tissue, most PSM genes were predominantly overexpressed in cancer. Survival analysis also established a relationship with PSM gene expression and adverse clinical outcome, where PSMA1 and PSMD11 expression were linked to more unfavorable prognosis in ≥ 30% of cancer types for both overall survival (OS) and relapse-free interval (PFI). Interestingly, PSMB5 gene expression was associated with OS (36%) and PFI (27%), and OS for PSMD2 (42%), especially when overexpressed.
CONCLUSION
CONCLUSIONS
These findings indicate that several PSM genes may potentially be prognostic biomarkers and novel therapeutic targets for different cancer forms.
Identifiants
pubmed: 36123629
doi: 10.1186/s12885-022-10079-4
pii: 10.1186/s12885-022-10079-4
pmc: PMC9484138
doi:
Substances chimiques
Biomarkers
0
DNA
9007-49-2
Proteasome Endopeptidase Complex
EC 3.4.25.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
993Subventions
Organisme : Stiftelsen Assar Gabrielssons Fond
ID : FB19-04
Organisme : Cancerfonden
ID : CAN2018/471
Organisme : Stiftelsen Jubileumsklinikens Forskningsfond mot Cancer
ID : 2020:295
Organisme : The Swedish Society of Medicine
ID : SLS-935552
Informations de copyright
© 2022. The Author(s).
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