Identify truly high-risk TP53-mutated diffuse large B cell lymphoma patients and explore the underlying biological mechanisms
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 fr...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
BioMed Central
2024
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| _version_ | 1811140933276663808 |
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| author | Du, K Wu, Y Hua, W Duan, Z Gao, R Liang, J Li, Y Yin, H Wu, J Shen, H Wang, L Shao, Y Li, J Liang, J Xu, W |
| author_facet | Du, K Wu, Y Hua, W Duan, Z Gao, R Liang, J Li, Y Yin, H Wu, J Shen, H Wang, L Shao, Y Li, J Liang, J Xu, W |
| author_sort | Du, K |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-09-25T04:29:51Z |
| format | Journal article |
| id | oxford-uuid:748754f1-e454-4f31-8588-19b42eeacc65 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:29:51Z |
| publishDate | 2024 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | oxford-uuid:748754f1-e454-4f31-8588-19b42eeacc652024-08-24T20:03:52ZIdentify truly high-risk TP53-mutated diffuse large B cell lymphoma patients and explore the underlying biological mechanismsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:748754f1-e454-4f31-8588-19b42eeacc65EnglishJisc Publications RouterBioMed Central2024Du, KWu, YHua, WDuan, ZGao, RLiang, JLi, YYin, HWu, JShen, HWang, LShao, YLi, JLiang, JXu, WTP53 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. |
| spellingShingle | Du, K Wu, Y Hua, W Duan, Z Gao, R Liang, J Li, Y Yin, H Wu, J Shen, H Wang, L Shao, Y Li, J Liang, J Xu, W Identify truly high-risk TP53-mutated diffuse large B cell lymphoma patients and explore the underlying biological mechanisms |
| title | Identify truly high-risk TP53-mutated diffuse large B cell lymphoma patients and explore the underlying biological mechanisms |
| title_full | Identify truly high-risk TP53-mutated diffuse large B cell lymphoma patients and explore the underlying biological mechanisms |
| title_fullStr | Identify truly high-risk TP53-mutated diffuse large B cell lymphoma patients and explore the underlying biological mechanisms |
| title_full_unstemmed | Identify truly high-risk TP53-mutated diffuse large B cell lymphoma patients and explore the underlying biological mechanisms |
| title_short | Identify truly high-risk TP53-mutated diffuse large B cell lymphoma patients and explore the underlying biological mechanisms |
| title_sort | identify truly high risk tp53 mutated diffuse large b cell lymphoma patients and explore the underlying biological mechanisms |
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