An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer.
Aged
BCG Vaccine
/ administration & dosage
Biomarkers, Tumor
/ genetics
Carcinoma, Transitional Cell
/ genetics
Chromosomal Instability
Cystectomy
/ methods
Denmark
/ epidemiology
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Genomics
Humans
Kaplan-Meier Estimate
Male
Mutation
Neoplasm Recurrence, Local
/ epidemiology
Prognosis
Progression-Free Survival
RNA-Seq
Urinary Bladder
/ immunology
Urinary Bladder Neoplasms
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 04 2021
16 04 2021
Historique:
received:
11
06
2020
accepted:
09
03
2021
entrez:
17
4
2021
pubmed:
18
4
2021
medline:
4
5
2021
Statut:
epublish
Résumé
The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n = 834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations are significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration is associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirms the higher infiltration of class 2b tumors and demonstrates an association between higher immune cell infiltration and lower recurrence rates. Finally, the independent prognostic value of the transcriptomic classes is documented in 1228 validation samples using a single sample classification tool. The classifier provides a framework for biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials.
Identifiants
pubmed: 33863885
doi: 10.1038/s41467-021-22465-w
pii: 10.1038/s41467-021-22465-w
pmc: PMC8052448
doi:
Substances chimiques
BCG Vaccine
0
Biomarkers, Tumor
0
Types de publication
Journal Article
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
2301Subventions
Organisme : BLRD VA
ID : I01 BX005599
Pays : United States
Commentaires et corrections
Type : CommentIn
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