BEND4: a novel prognostic biomarker in diffuse large B-cell lymphoma

Abstract Background BEN domain-containing protein 4 (BEND4) is implicated in various cancer-related processes, but its role in diffuse large B-cell lymphoma (DLBCL) remains unclear. This study examined BEND4’s impact on DLBCL prognosis through bioinformatics analysis. Methods BEND4 expression was an...

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Main Authors: Yanfang Wang, Zhenhao Zhang, Lianyong Xi, Hua Wang, Fei Dong
Format: Article
Language:English
Published: Springer 2025-05-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-02519-x
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author Yanfang Wang
Zhenhao Zhang
Lianyong Xi
Hua Wang
Fei Dong
author_facet Yanfang Wang
Zhenhao Zhang
Lianyong Xi
Hua Wang
Fei Dong
author_sort Yanfang Wang
collection DOAJ
description Abstract Background BEN domain-containing protein 4 (BEND4) is implicated in various cancer-related processes, but its role in diffuse large B-cell lymphoma (DLBCL) remains unclear. This study examined BEND4’s impact on DLBCL prognosis through bioinformatics analysis. Methods BEND4 expression was analyzed across the cancer cell line encyclopedia (CCLE), human protein atlas (HPA), and the cancer genome atlas (TCGA) databases. Associations between BEND4 expression and survival outcomes, prognosis, and immune infiltration levels of DLBCL were evaluated via TCGA. Gene set enrichment analysis (GSEA) identified potential BEND4 biological functions. The predictive value of BEND4 and related genes for DLBCL mortality was assessed using time-dependent receiver operating characteristic curve (ROC) analysis. Findings were validated through qRT-PCR and cell proliferation assays. Results BEND4 was overexpressed at mRNA and protein levels in DLBCL. High BEND4 expression correlated with shorter survival, higher disease-specific mortality, and poor prognosis, emerging as an independent risk factor. GSEA revealed associations between BEND4 and chromatin remodeling, immune response, epigenetic regulation, and signal transduction. Immune infiltration analysis showed BEND4 expression was inversely correlated with eosinophils, cytotoxic cells, and Tgd cells infiltration. ROC analysis confirmed BEND4 and related genes as key predictors of DLBCL mortality at 1, 3, and 5 years. In vitro, BEND4 inhibition did not alter Riva cells proliferation but enhanced sensitivity of Riva cells to chemotherapy, including doxorubicin. Conclusion Elevated BEND4 levels were linked to poor prognosis and chemoresistance in DLBCL, potentially due to transcriptional regulation and immune suppression roles. BEND4 may represent a viable therapeutic target in DLBCL.
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spelling doaj-art-d25e85f3adc3438db585e8d72ff0ff942025-08-20T03:09:20ZengSpringerDiscover Oncology2730-60112025-05-0116111310.1007/s12672-025-02519-xBEND4: a novel prognostic biomarker in diffuse large B-cell lymphomaYanfang Wang0Zhenhao Zhang1Lianyong Xi2Hua Wang3Fei Dong4Department of Hematology, Lymphoma Research Center, Peking University Third HospitalDepartment of Hematology, Lymphoma Research Center, Peking University Third HospitalDepartment of Hematology, Lymphoma Research Center, Peking University Third HospitalDepartment of Hematology, Lymphoma Research Center, Peking University Third HospitalDepartment of Hematology, Lymphoma Research Center, Peking University Third HospitalAbstract Background BEN domain-containing protein 4 (BEND4) is implicated in various cancer-related processes, but its role in diffuse large B-cell lymphoma (DLBCL) remains unclear. This study examined BEND4’s impact on DLBCL prognosis through bioinformatics analysis. Methods BEND4 expression was analyzed across the cancer cell line encyclopedia (CCLE), human protein atlas (HPA), and the cancer genome atlas (TCGA) databases. Associations between BEND4 expression and survival outcomes, prognosis, and immune infiltration levels of DLBCL were evaluated via TCGA. Gene set enrichment analysis (GSEA) identified potential BEND4 biological functions. The predictive value of BEND4 and related genes for DLBCL mortality was assessed using time-dependent receiver operating characteristic curve (ROC) analysis. Findings were validated through qRT-PCR and cell proliferation assays. Results BEND4 was overexpressed at mRNA and protein levels in DLBCL. High BEND4 expression correlated with shorter survival, higher disease-specific mortality, and poor prognosis, emerging as an independent risk factor. GSEA revealed associations between BEND4 and chromatin remodeling, immune response, epigenetic regulation, and signal transduction. Immune infiltration analysis showed BEND4 expression was inversely correlated with eosinophils, cytotoxic cells, and Tgd cells infiltration. ROC analysis confirmed BEND4 and related genes as key predictors of DLBCL mortality at 1, 3, and 5 years. In vitro, BEND4 inhibition did not alter Riva cells proliferation but enhanced sensitivity of Riva cells to chemotherapy, including doxorubicin. Conclusion Elevated BEND4 levels were linked to poor prognosis and chemoresistance in DLBCL, potentially due to transcriptional regulation and immune suppression roles. BEND4 may represent a viable therapeutic target in DLBCL.https://doi.org/10.1007/s12672-025-02519-xBEND4Diffuse large B-cell lymphomaTCGABiomarkerPrognosisImmune infiltration
spellingShingle Yanfang Wang
Zhenhao Zhang
Lianyong Xi
Hua Wang
Fei Dong
BEND4: a novel prognostic biomarker in diffuse large B-cell lymphoma
Discover Oncology
BEND4
Diffuse large B-cell lymphoma
TCGA
Biomarker
Prognosis
Immune infiltration
title BEND4: a novel prognostic biomarker in diffuse large B-cell lymphoma
title_full BEND4: a novel prognostic biomarker in diffuse large B-cell lymphoma
title_fullStr BEND4: a novel prognostic biomarker in diffuse large B-cell lymphoma
title_full_unstemmed BEND4: a novel prognostic biomarker in diffuse large B-cell lymphoma
title_short BEND4: a novel prognostic biomarker in diffuse large B-cell lymphoma
title_sort bend4 a novel prognostic biomarker in diffuse large b cell lymphoma
topic BEND4
Diffuse large B-cell lymphoma
TCGA
Biomarker
Prognosis
Immune infiltration
url https://doi.org/10.1007/s12672-025-02519-x
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AT zhenhaozhang bend4anovelprognosticbiomarkerindiffuselargebcelllymphoma
AT lianyongxi bend4anovelprognosticbiomarkerindiffuselargebcelllymphoma
AT huawang bend4anovelprognosticbiomarkerindiffuselargebcelllymphoma
AT feidong bend4anovelprognosticbiomarkerindiffuselargebcelllymphoma