The Dark Side of Pyroptosis of Diffuse Large B-Cell Lymphoma in B-Cell Non-Hodgkin Lymphoma: Mediating the Specific Inflammatory Microenvironment

Background: Diffuse large B-cell lymphoma (DLBCL) is a common aggressive B-cell non-Hodgkin lymphoma (B-NHL). While combined chemotherapy has improved the outcomes of DLBCL, it remains a highly detrimental disease. Pyroptosis, an inflammatory programmed cell death, is considered to have both tumor-p...

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Autores principales: Wei Wang, Shi-wen Xu, Ya Teng, Min Zhu, Qun-yi Guo, Yuan-wen Wang, Xin-Li Mao, Shao-wei Li, Wen-da Luo
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:1204a189b31247a287bf6e1c45b429992021-11-05T08:16:58ZThe Dark Side of Pyroptosis of Diffuse Large B-Cell Lymphoma in B-Cell Non-Hodgkin Lymphoma: Mediating the Specific Inflammatory Microenvironment2296-634X10.3389/fcell.2021.779123https://doaj.org/article/1204a189b31247a287bf6e1c45b429992021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.779123/fullhttps://doaj.org/toc/2296-634XBackground: Diffuse large B-cell lymphoma (DLBCL) is a common aggressive B-cell non-Hodgkin lymphoma (B-NHL). While combined chemotherapy has improved the outcomes of DLBCL, it remains a highly detrimental disease. Pyroptosis, an inflammatory programmed cell death, is considered to have both tumor-promoting and tumor-suppressing effects. The role of pyroptosis in DLBCL has been gradually appreciated, but its value needs further investigation.Methods: We analyzed mutations and copy number variation (CNV) alterations of pyroptosis-related genes (PRGs) from The Cancer Genome Atlas (TCGA) cohort and evaluated the differences in expression in normal B cells and DLBCL patients in two Gene Expression Omnibus (GEO) datasets (GSE12195 and GSE56315). Based on the expression of 52 PRGs, we divided 421 DLBCL patients from the GSE31312 dataset into distinct clusters using consensus clustering. The Kaplan-Meier method was used to prognosis among the three clusters, and GSVA was used to explore differences in the biological functions. ESTIMATE and single-sample gene-set enrichment analysis (ssGSEA) were used to analyze the tumor immune microenvironment (TME) in different clusters. A risk score signature was developed using a univariate survival analysis and multivariate regression analysis, and the reliability and validity of the signature were verified. By combining the signature with clinical factors, a nomogram was established to predict the prognosis of DLBCL patients. The alluvial diagram and correlation matrix were used to explore the relationship between pyroptosis risk score, clinical features and TME.Results: A large proportion of PRGs are dysregulated in DLBCL and associated with the prognosis. We found three distinct pyroptosis-related clusters (cluster A, B, and C) that differed significantly with regard to the prognosis, biological process, clinical characteristics, chemotherapeutic drug sensitivity, and TME. Furthermore, we developed a risk score signature that effectively differentiates high and low-risk patients. The nomogram combining this signature with several clinical indicators showed an excellent ability to predict the prognosis of DCBCL patients.Conclusions: This work demonstrates that pyroptosis plays an important role in the diversity and complexity of the TME in DLBCL. The risk signature of pyroptosis is a promising predictive tool. A correct and comprehensive assessment of the mode of action of pyroptosis in individuals will help guide more effective treatment.Wei WangShi-wen XuYa TengMin ZhuQun-yi GuoQun-yi GuoYuan-wen WangYuan-wen WangXin-Li MaoXin-Li MaoXin-Li MaoShao-wei LiShao-wei LiShao-wei LiWen-da LuoWen-da LuoWen-da LuoFrontiers Media S.A.articlepyroptosisdiffuse large B-cell lymphomatumor immune microenvironmentinflammationprognosisBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution DOAJ
collection DOAJ
language EN
topic pyroptosis
diffuse large B-cell lymphoma
tumor immune microenvironment
inflammation
prognosis
Biology (General)
QH301-705.5
spellingShingle pyroptosis
diffuse large B-cell lymphoma
tumor immune microenvironment
inflammation
prognosis
Biology (General)
QH301-705.5
Wei Wang
Shi-wen Xu
Ya Teng
Min Zhu
Qun-yi Guo
Qun-yi Guo
Yuan-wen Wang
Yuan-wen Wang
Xin-Li Mao
Xin-Li Mao
Xin-Li Mao
Shao-wei Li
Shao-wei Li
Shao-wei Li
Wen-da Luo
Wen-da Luo
Wen-da Luo
The Dark Side of Pyroptosis of Diffuse Large B-Cell Lymphoma in B-Cell Non-Hodgkin Lymphoma: Mediating the Specific Inflammatory Microenvironment
description Background: Diffuse large B-cell lymphoma (DLBCL) is a common aggressive B-cell non-Hodgkin lymphoma (B-NHL). While combined chemotherapy has improved the outcomes of DLBCL, it remains a highly detrimental disease. Pyroptosis, an inflammatory programmed cell death, is considered to have both tumor-promoting and tumor-suppressing effects. The role of pyroptosis in DLBCL has been gradually appreciated, but its value needs further investigation.Methods: We analyzed mutations and copy number variation (CNV) alterations of pyroptosis-related genes (PRGs) from The Cancer Genome Atlas (TCGA) cohort and evaluated the differences in expression in normal B cells and DLBCL patients in two Gene Expression Omnibus (GEO) datasets (GSE12195 and GSE56315). Based on the expression of 52 PRGs, we divided 421 DLBCL patients from the GSE31312 dataset into distinct clusters using consensus clustering. The Kaplan-Meier method was used to prognosis among the three clusters, and GSVA was used to explore differences in the biological functions. ESTIMATE and single-sample gene-set enrichment analysis (ssGSEA) were used to analyze the tumor immune microenvironment (TME) in different clusters. A risk score signature was developed using a univariate survival analysis and multivariate regression analysis, and the reliability and validity of the signature were verified. By combining the signature with clinical factors, a nomogram was established to predict the prognosis of DLBCL patients. The alluvial diagram and correlation matrix were used to explore the relationship between pyroptosis risk score, clinical features and TME.Results: A large proportion of PRGs are dysregulated in DLBCL and associated with the prognosis. We found three distinct pyroptosis-related clusters (cluster A, B, and C) that differed significantly with regard to the prognosis, biological process, clinical characteristics, chemotherapeutic drug sensitivity, and TME. Furthermore, we developed a risk score signature that effectively differentiates high and low-risk patients. The nomogram combining this signature with several clinical indicators showed an excellent ability to predict the prognosis of DCBCL patients.Conclusions: This work demonstrates that pyroptosis plays an important role in the diversity and complexity of the TME in DLBCL. The risk signature of pyroptosis is a promising predictive tool. A correct and comprehensive assessment of the mode of action of pyroptosis in individuals will help guide more effective treatment.
format article
author Wei Wang
Shi-wen Xu
Ya Teng
Min Zhu
Qun-yi Guo
Qun-yi Guo
Yuan-wen Wang
Yuan-wen Wang
Xin-Li Mao
Xin-Li Mao
Xin-Li Mao
Shao-wei Li
Shao-wei Li
Shao-wei Li
Wen-da Luo
Wen-da Luo
Wen-da Luo
author_facet Wei Wang
Shi-wen Xu
Ya Teng
Min Zhu
Qun-yi Guo
Qun-yi Guo
Yuan-wen Wang
Yuan-wen Wang
Xin-Li Mao
Xin-Li Mao
Xin-Li Mao
Shao-wei Li
Shao-wei Li
Shao-wei Li
Wen-da Luo
Wen-da Luo
Wen-da Luo
author_sort Wei Wang
title The Dark Side of Pyroptosis of Diffuse Large B-Cell Lymphoma in B-Cell Non-Hodgkin Lymphoma: Mediating the Specific Inflammatory Microenvironment
title_short The Dark Side of Pyroptosis of Diffuse Large B-Cell Lymphoma in B-Cell Non-Hodgkin Lymphoma: Mediating the Specific Inflammatory Microenvironment
title_full The Dark Side of Pyroptosis of Diffuse Large B-Cell Lymphoma in B-Cell Non-Hodgkin Lymphoma: Mediating the Specific Inflammatory Microenvironment
title_fullStr The Dark Side of Pyroptosis of Diffuse Large B-Cell Lymphoma in B-Cell Non-Hodgkin Lymphoma: Mediating the Specific Inflammatory Microenvironment
title_full_unstemmed The Dark Side of Pyroptosis of Diffuse Large B-Cell Lymphoma in B-Cell Non-Hodgkin Lymphoma: Mediating the Specific Inflammatory Microenvironment
title_sort dark side of pyroptosis of diffuse large b-cell lymphoma in b-cell non-hodgkin lymphoma: mediating the specific inflammatory microenvironment
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/1204a189b31247a287bf6e1c45b42999
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