Integrative analysis of a necroptosis-related gene signature of clinical value and heterogeneity in diffuse large B cell lymphoma
Background: Diffuse large B-cell lymphoma (DLBCL), which is considered to be the most common subtype of lymphoma, is an aggressive tumor. Necroptosis, a novel type of programmed cell death, plays a bidirectional role in tumors and participates in the tumor microenvironment to influence tumor develop...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.911443/full |
| _version_ | 1811308780236832768 |
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| author | Yu-Biao Pan Yu-Biao Pan Wei Wang Wei Wang Hong-Kai Cai Hong-Kai Cai Jia Zhang Jia Zhang Ya Teng Jiji Xue Min Zhu Wen-Da Luo Wen-Da Luo Wen-Da Luo |
| author_facet | Yu-Biao Pan Yu-Biao Pan Wei Wang Wei Wang Hong-Kai Cai Hong-Kai Cai Jia Zhang Jia Zhang Ya Teng Jiji Xue Min Zhu Wen-Da Luo Wen-Da Luo Wen-Da Luo |
| author_sort | Yu-Biao Pan |
| collection | DOAJ |
| description | Background: Diffuse large B-cell lymphoma (DLBCL), which is considered to be the most common subtype of lymphoma, is an aggressive tumor. Necroptosis, a novel type of programmed cell death, plays a bidirectional role in tumors and participates in the tumor microenvironment to influence tumor development. Targeting necroptosis is an intriguing direction, whereas its role in DLBCL needs to be further discussed.Methods: We obtained 17 DLBCL-associated necroptosis-related genes by univariate cox regression screening. We clustered in GSE31312 depending on their expressions of these 17 genes and analyzed the differences in clinical characteristics between different clusters. To investigate the differences in prognosis across distinct clusters, the Kaplan-Meier method was utilized. The variations in the tumor immune microenvironment (TME) between distinct necroptosis-related clusters were investigated via “ESTIMATE”, “Cibersort” and single-sample geneset enrichment analysis (ssGSEA). Finally, we constructed a 6-gene prognostic model by lasso-cox regression and subsequently integrated clinical features to construct a prognostic nomogram.Results: Our analysis indicated stable but distinct mechanism of action of necroptosis in DLBCL. Based on necroptosis-related genes and cluster-associated genes, we identified three groups of patients with significant differences in prognosis, TME, and chemotherapy drug sensitivity. Analysis of immune infiltration in the TME showed that cluster 1, which displayed the best prognosis, was significantly infiltrated by natural killer T cells, dendritic cells, CD8+ T cells, and M1 macrophages. Cluster 3 presented M2 macrophage infiltration and the worst prognosis. Importantly, the prognostic model successfully differentiated high-risk from low-risk patients, and could forecast the survival of DLBCL patients. And the constructed nomogram demonstrated a remarkable capacity to forecast the survival time of DLBCL patients after incorporating predictive clinical characteristics.Conclusion: The different patterns of necroptosis explain its role in regulating the immune microenvironment of DLBCL and the response to R-CHOP treatment. Systematic assessment of necroptosis patterns in patients with DLBCL will help us understand the characteristics of tumor microenvironment cell infiltration and aid in the development of tailored therapy regimens. |
| first_indexed | 2024-04-13T09:29:26Z |
| format | Article |
| id | doaj.art-cfaa792e418847f9af213b02bd998550 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-13T09:29:26Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-cfaa792e418847f9af213b02bd9985502022-12-22T02:52:19ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-08-011310.3389/fgene.2022.911443911443Integrative analysis of a necroptosis-related gene signature of clinical value and heterogeneity in diffuse large B cell lymphomaYu-Biao Pan0Yu-Biao Pan1Wei Wang2Wei Wang3Hong-Kai Cai4Hong-Kai Cai5Jia Zhang6Jia Zhang7Ya Teng8Jiji Xue9Min Zhu10Wen-Da Luo11Wen-Da Luo12Wen-Da Luo13Taizhou Hospital of Zhejiang Province, Zhejiang University, Hangzhoua, ChinaDepartment of Hematology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, ChinaDepartment of Hematology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, ChinaTaizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, ChinaDepartment of Hematology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, ChinaTaizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, ChinaDepartment of Hematology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, ChinaTaizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, ChinaTaizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, ChinaTaizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, ChinaTaizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, ChinaTaizhou Hospital of Zhejiang Province, Zhejiang University, Hangzhoua, ChinaDepartment of Hematology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, ChinaTaizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, ChinaBackground: Diffuse large B-cell lymphoma (DLBCL), which is considered to be the most common subtype of lymphoma, is an aggressive tumor. Necroptosis, a novel type of programmed cell death, plays a bidirectional role in tumors and participates in the tumor microenvironment to influence tumor development. Targeting necroptosis is an intriguing direction, whereas its role in DLBCL needs to be further discussed.Methods: We obtained 17 DLBCL-associated necroptosis-related genes by univariate cox regression screening. We clustered in GSE31312 depending on their expressions of these 17 genes and analyzed the differences in clinical characteristics between different clusters. To investigate the differences in prognosis across distinct clusters, the Kaplan-Meier method was utilized. The variations in the tumor immune microenvironment (TME) between distinct necroptosis-related clusters were investigated via “ESTIMATE”, “Cibersort” and single-sample geneset enrichment analysis (ssGSEA). Finally, we constructed a 6-gene prognostic model by lasso-cox regression and subsequently integrated clinical features to construct a prognostic nomogram.Results: Our analysis indicated stable but distinct mechanism of action of necroptosis in DLBCL. Based on necroptosis-related genes and cluster-associated genes, we identified three groups of patients with significant differences in prognosis, TME, and chemotherapy drug sensitivity. Analysis of immune infiltration in the TME showed that cluster 1, which displayed the best prognosis, was significantly infiltrated by natural killer T cells, dendritic cells, CD8+ T cells, and M1 macrophages. Cluster 3 presented M2 macrophage infiltration and the worst prognosis. Importantly, the prognostic model successfully differentiated high-risk from low-risk patients, and could forecast the survival of DLBCL patients. And the constructed nomogram demonstrated a remarkable capacity to forecast the survival time of DLBCL patients after incorporating predictive clinical characteristics.Conclusion: The different patterns of necroptosis explain its role in regulating the immune microenvironment of DLBCL and the response to R-CHOP treatment. Systematic assessment of necroptosis patterns in patients with DLBCL will help us understand the characteristics of tumor microenvironment cell infiltration and aid in the development of tailored therapy regimens.https://www.frontiersin.org/articles/10.3389/fgene.2022.911443/fulldiffuse large B-cell lymphomanecroptosisprognosisTMEimmunization |
| spellingShingle | Yu-Biao Pan Yu-Biao Pan Wei Wang Wei Wang Hong-Kai Cai Hong-Kai Cai Jia Zhang Jia Zhang Ya Teng Jiji Xue Min Zhu Wen-Da Luo Wen-Da Luo Wen-Da Luo Integrative analysis of a necroptosis-related gene signature of clinical value and heterogeneity in diffuse large B cell lymphoma Frontiers in Genetics diffuse large B-cell lymphoma necroptosis prognosis TME immunization |
| title | Integrative analysis of a necroptosis-related gene signature of clinical value and heterogeneity in diffuse large B cell lymphoma |
| title_full | Integrative analysis of a necroptosis-related gene signature of clinical value and heterogeneity in diffuse large B cell lymphoma |
| title_fullStr | Integrative analysis of a necroptosis-related gene signature of clinical value and heterogeneity in diffuse large B cell lymphoma |
| title_full_unstemmed | Integrative analysis of a necroptosis-related gene signature of clinical value and heterogeneity in diffuse large B cell lymphoma |
| title_short | Integrative analysis of a necroptosis-related gene signature of clinical value and heterogeneity in diffuse large B cell lymphoma |
| title_sort | integrative analysis of a necroptosis related gene signature of clinical value and heterogeneity in diffuse large b cell lymphoma |
| topic | diffuse large B-cell lymphoma necroptosis prognosis TME immunization |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.911443/full |
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