Refining prognostic assessment of diffuse large B-cell lymphoma: insights from multi-omics and single-cell analysis unveil SRM as a key target for regulating immunotherapy
Abstract Purposes Previous studies have demonstrated that proliferation, stroma or immunity strongly influence the prognosis and therapeutic resistance of diffuse large B-cell lymphoma (DLBCL). Herein, we aimed to integrate proliferation, stromal, and immune (PSI) features to systematically evaluate...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SpringerOpen
2025-01-01
|
| Series: | Journal of Big Data |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40537-025-01067-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832585670603833344 |
|---|---|
| author | Xiaojie Liang Jia Guo Baiwei Luo Weixiang Lu Qiumin Chen Yeling Deng Yunong Yang Liang Wang |
| author_facet | Xiaojie Liang Jia Guo Baiwei Luo Weixiang Lu Qiumin Chen Yeling Deng Yunong Yang Liang Wang |
| author_sort | Xiaojie Liang |
| collection | DOAJ |
| description | Abstract Purposes Previous studies have demonstrated that proliferation, stroma or immunity strongly influence the prognosis and therapeutic resistance of diffuse large B-cell lymphoma (DLBCL). Herein, we aimed to integrate proliferation, stromal, and immune (PSI) features to systematically evaluate the risk stratification and explore novel therapeutic targets in DLBCL. Methods Using data from multiple researches, we comprehensively evaluated the characteristics and prognostic impact of PSI features in DLBCL, and developed a novel risk stratification model (PSI score) with a consistent cutoff value to stratify the risk of 3,229 DLBCL patients from different cohorts. Mechanisms underlying adverse prognosis in the high-risk DLBCLs were investigated through transcriptomic (n = 3,229), genomic (n = 576), and scRNA-seq (n = 20) analyses. Results We identified a high-risk DLBCL subgroup (HPSI, 36.1% of DLBCL). HPSI was characterized by upregulation of spermidine synthase (SRM) and cold tumor microenvironment (TME). Compared to low-risk group, HPSI exhibited poorer prognosis, with lower 3-year OS (51.7% vs. 78.1%, P < 0.0001) and PFS (48.9% vs. 72.6%, P < 0.0001) rates. HPSI shared malignant proliferative phenotype resembling Burkitt lymphoma. Genomic analysis revealed extensive copy-number loss in the chemokine and interleukin coding regions within HPSI. Bulk and scRNA-seq analyses indicated that upregulation of SRM might mediate cold TME in DLBCL, potentially through suppressing immune activation pathways, promoting dendritic cells (DCs) transformation into tolerogenic DCs, and facilitating M2 polarization of macrophages. Finally, for eventual clinical translation, we integrated the model with other clinical features to develop a comprehensive database for DLBCL. Conclusion Our study effectively simplifies risk stratification of DLBCL, revealing that immune microenvironment and SRM jointly shape a subgroup of DLBCL with extremely poor prognosis. Targeting SRM may become a potential strategy for modulating immunotherapy in DLBCL, providing new insight for immunotherapy. |
| format | Article |
| id | doaj-art-d4f79defec8747e782a17662bbcfd568 |
| institution | Kabale University |
| issn | 2196-1115 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Journal of Big Data |
| spelling | doaj-art-d4f79defec8747e782a17662bbcfd5682025-01-26T12:37:43ZengSpringerOpenJournal of Big Data2196-11152025-01-0112112510.1186/s40537-025-01067-zRefining prognostic assessment of diffuse large B-cell lymphoma: insights from multi-omics and single-cell analysis unveil SRM as a key target for regulating immunotherapyXiaojie Liang0Jia Guo1Baiwei Luo2Weixiang Lu3Qiumin Chen4Yeling Deng5Yunong Yang6Liang Wang7Department of Hematology, Beijing Tongren Hospital, Capital Medical UniversityDepartment of Hematology, Beijing Tongren Hospital, Capital Medical UniversityDepartment of Hematology, Nanfang Hospital, Southern Medical UniversityDepartment of Hematology, Beijing Tongren Hospital, Capital Medical UniversityThe First School of Clinical Medicine, Guangdong Medical UniversityThe First School of Clinical Medicine, Guangdong Medical UniversityThe First School of Clinical Medicine, Guangdong Medical UniversityDepartment of Hematology, Beijing Tongren Hospital, Capital Medical UniversityAbstract Purposes Previous studies have demonstrated that proliferation, stroma or immunity strongly influence the prognosis and therapeutic resistance of diffuse large B-cell lymphoma (DLBCL). Herein, we aimed to integrate proliferation, stromal, and immune (PSI) features to systematically evaluate the risk stratification and explore novel therapeutic targets in DLBCL. Methods Using data from multiple researches, we comprehensively evaluated the characteristics and prognostic impact of PSI features in DLBCL, and developed a novel risk stratification model (PSI score) with a consistent cutoff value to stratify the risk of 3,229 DLBCL patients from different cohorts. Mechanisms underlying adverse prognosis in the high-risk DLBCLs were investigated through transcriptomic (n = 3,229), genomic (n = 576), and scRNA-seq (n = 20) analyses. Results We identified a high-risk DLBCL subgroup (HPSI, 36.1% of DLBCL). HPSI was characterized by upregulation of spermidine synthase (SRM) and cold tumor microenvironment (TME). Compared to low-risk group, HPSI exhibited poorer prognosis, with lower 3-year OS (51.7% vs. 78.1%, P < 0.0001) and PFS (48.9% vs. 72.6%, P < 0.0001) rates. HPSI shared malignant proliferative phenotype resembling Burkitt lymphoma. Genomic analysis revealed extensive copy-number loss in the chemokine and interleukin coding regions within HPSI. Bulk and scRNA-seq analyses indicated that upregulation of SRM might mediate cold TME in DLBCL, potentially through suppressing immune activation pathways, promoting dendritic cells (DCs) transformation into tolerogenic DCs, and facilitating M2 polarization of macrophages. Finally, for eventual clinical translation, we integrated the model with other clinical features to develop a comprehensive database for DLBCL. Conclusion Our study effectively simplifies risk stratification of DLBCL, revealing that immune microenvironment and SRM jointly shape a subgroup of DLBCL with extremely poor prognosis. Targeting SRM may become a potential strategy for modulating immunotherapy in DLBCL, providing new insight for immunotherapy.https://doi.org/10.1186/s40537-025-01067-zDLBCLProliferationStromalImmuneRisk stratificationSRM |
| spellingShingle | Xiaojie Liang Jia Guo Baiwei Luo Weixiang Lu Qiumin Chen Yeling Deng Yunong Yang Liang Wang Refining prognostic assessment of diffuse large B-cell lymphoma: insights from multi-omics and single-cell analysis unveil SRM as a key target for regulating immunotherapy Journal of Big Data DLBCL Proliferation Stromal Immune Risk stratification SRM |
| title | Refining prognostic assessment of diffuse large B-cell lymphoma: insights from multi-omics and single-cell analysis unveil SRM as a key target for regulating immunotherapy |
| title_full | Refining prognostic assessment of diffuse large B-cell lymphoma: insights from multi-omics and single-cell analysis unveil SRM as a key target for regulating immunotherapy |
| title_fullStr | Refining prognostic assessment of diffuse large B-cell lymphoma: insights from multi-omics and single-cell analysis unveil SRM as a key target for regulating immunotherapy |
| title_full_unstemmed | Refining prognostic assessment of diffuse large B-cell lymphoma: insights from multi-omics and single-cell analysis unveil SRM as a key target for regulating immunotherapy |
| title_short | Refining prognostic assessment of diffuse large B-cell lymphoma: insights from multi-omics and single-cell analysis unveil SRM as a key target for regulating immunotherapy |
| title_sort | refining prognostic assessment of diffuse large b cell lymphoma insights from multi omics and single cell analysis unveil srm as a key target for regulating immunotherapy |
| topic | DLBCL Proliferation Stromal Immune Risk stratification SRM |
| url | https://doi.org/10.1186/s40537-025-01067-z |
| work_keys_str_mv | AT xiaojieliang refiningprognosticassessmentofdiffuselargebcelllymphomainsightsfrommultiomicsandsinglecellanalysisunveilsrmasakeytargetforregulatingimmunotherapy AT jiaguo refiningprognosticassessmentofdiffuselargebcelllymphomainsightsfrommultiomicsandsinglecellanalysisunveilsrmasakeytargetforregulatingimmunotherapy AT baiweiluo refiningprognosticassessmentofdiffuselargebcelllymphomainsightsfrommultiomicsandsinglecellanalysisunveilsrmasakeytargetforregulatingimmunotherapy AT weixianglu refiningprognosticassessmentofdiffuselargebcelllymphomainsightsfrommultiomicsandsinglecellanalysisunveilsrmasakeytargetforregulatingimmunotherapy AT qiuminchen refiningprognosticassessmentofdiffuselargebcelllymphomainsightsfrommultiomicsandsinglecellanalysisunveilsrmasakeytargetforregulatingimmunotherapy AT yelingdeng refiningprognosticassessmentofdiffuselargebcelllymphomainsightsfrommultiomicsandsinglecellanalysisunveilsrmasakeytargetforregulatingimmunotherapy AT yunongyang refiningprognosticassessmentofdiffuselargebcelllymphomainsightsfrommultiomicsandsinglecellanalysisunveilsrmasakeytargetforregulatingimmunotherapy AT liangwang refiningprognosticassessmentofdiffuselargebcelllymphomainsightsfrommultiomicsandsinglecellanalysisunveilsrmasakeytargetforregulatingimmunotherapy |