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Published on: February 12, 2022
BEND4: a novel prognostic biomarker in diffuse large B-cell lymphoma
Yanfang Wang1, Zhenhao Zhang1, Lianyong Xi1
1Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, No. 49 Huayuan North Road, Beijing, 100191, China.
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.
Insights
BEN domain-containing protein 4 (BEND4) is overexpressed in diffuse large B-cell lymphoma (DLBCL), correlating with poor prognosis and chemoresistance. BEND4 may be a therapeutic target for DLBCL treatment.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- BEN domain-containing protein 4 (BEND4) is involved in cancer, but its role in diffuse large B-cell lymphoma (DLBCL) is unknown.
- This study investigates the prognostic significance of BEND4 in DLBCL.
Purpose of the Study:
- To analyze BEND4 expression in DLBCL.
- To determine the association between BEND4 and DLBCL prognosis, survival, and immune infiltration.
- To explore BEND4's potential as a therapeutic target.
Main Methods:
- Bioinformatic analysis of BEND4 expression in CCLE, HPA, and TCGA databases.
- Correlation analysis of BEND4 with DLBCL survival, prognosis, and immune cell infiltration using TCGA data.
- Gene Set Enrichment Analysis (GSEA) and Receiver Operating Characteristic (ROC) curve analysis.
- In vitro validation using qRT-PCR and cell proliferation assays.
Main Results:
- BEND4 is overexpressed in DLBCL at mRNA and protein levels.
- High BEND4 expression is linked to shorter survival, increased mortality, and poor prognosis, acting as an independent risk factor.
- BEND4 correlates with chromatin remodeling, immune response, and epigenetic regulation, and is inversely associated with immune cell infiltration.
- BEND4 inhibition enhances DLBCL cell sensitivity to chemotherapy.
Conclusions:
- Elevated BEND4 expression in DLBCL is associated with poor prognosis and chemoresistance.
- BEND4's roles in transcriptional regulation and immune suppression contribute to its impact on DLBCL.
- BEND4 presents a potential therapeutic target for DLBCL treatment.
