Epigenetic and transcriptomic characterization reveals progression markers and essential pathways in clear cell renal cell carcinoma.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
27 03 2023
27 03 2023
Historique:
received:
14
10
2022
accepted:
07
03
2023
medline:
29
3
2023
entrez:
27
3
2023
pubmed:
28
3
2023
Statut:
epublish
Résumé
Identifying tumor-cell-specific markers and elucidating their epigenetic regulation and spatial heterogeneity provides mechanistic insights into cancer etiology. Here, we perform snRNA-seq and snATAC-seq in 34 and 28 human clear cell renal cell carcinoma (ccRCC) specimens, respectively, with matched bulk proteogenomics data. By identifying 20 tumor-specific markers through a multi-omics tiered approach, we reveal an association between higher ceruloplasmin (CP) expression and reduced survival. CP knockdown, combined with spatial transcriptomics, suggests a role for CP in regulating hyalinized stroma and tumor-stroma interactions in ccRCC. Intratumoral heterogeneity analysis portrays tumor cell-intrinsic inflammation and epithelial-mesenchymal transition (EMT) as two distinguishing features of tumor subpopulations. Finally, BAP1 mutations are associated with widespread reduction of chromatin accessibility, while PBRM1 mutations generally increase accessibility, with the former affecting five times more accessible peaks than the latter. These integrated analyses reveal the cellular architecture of ccRCC, providing insights into key markers and pathways in ccRCC tumorigenesis.
Identifiants
pubmed: 36973268
doi: 10.1038/s41467-023-37211-7
pii: 10.1038/s41467-023-37211-7
pmc: PMC10042888
doi:
Substances chimiques
Tumor Suppressor Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1681Subventions
Organisme : NHGRI NIH HHS
ID : R01 HG009711
Pays : United States
Organisme : NCI NIH HHS
ID : U2C CA233303
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA211006
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA210957
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2023. The Author(s).
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