Identify truly high-risk TP53-mutated diffuse large B cell lymphoma patients and explore the underlying biological mechanisms.
Cell Commun Signal
; 22(1): 401, 2024 Aug 15.
Article
in En
| MEDLINE
| ID: mdl-39148095
ABSTRACT
TP53 mutation (TP53-mut) correlates with inferior survival in many cancers, whereas its prognostic role in diffuse large B-cell lymphoma (DLBCL) is still in controversy. Therefore, more precise risk stratification needs to be further explored for TP53-mut DLBCL patients. A set of 2637 DLBCL cases from multiple cohorts, was enrolled in our analysis. Among the 2637 DLBCL patients, 14.0% patients (370/2637) had TP53-mut. Since missense mutations account for the vast majority of TP53-mut DLBCL patients, and most non-missense mutations affect the function of the P53 protein, leading to worse survival rates, we distinguished patients with missense mutations. A TP53 missense mutation risk model was constructed based on a 150-combination machine learning computational framework, demonstrating excellent performance in predicting prognosis. Further analysis revealed that patients with high-risk missense mutations are significantly associated with early progression and exhibit dysregulation of multiple immune and metabolic pathways at the transcriptional level. Additionally, the high-risk group showed an absolutely suppressed immune microenvironment. To stratify the entire cohort of TP53-mut DLBCL, we combined clinical characteristics and ultimately constructed the TP53 Prognostic Index (TP53PI) model. In summary, we identified the truly high-risk TP53-mut DLBCL patients and explained this difference at the mutation and transcriptional levels.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tumor Suppressor Protein p53
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Lymphoma, Large B-Cell, Diffuse
Limits:
Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
Cell Commun Signal
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: