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Comprehensive analysis of the prognostic implication and immune infiltration of CISD2 in diffuse large B-cell
ChaoFeng Zhang1,2,3, Qi Lin4, ChunTuan Li1
1Department of Haematology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, China.
Insights
High expression of CDGSH iron sulfur domain 2 (CISD2) in diffuse large B-cell lymphoma (DLBCL) correlates with poor prognosis. A novel 27-gene risk score (CISD2Risk) effectively predicts outcomes and monitors treatment efficacy in DLBCL patients.
Area of Science:
- Oncology
- Hematology
- Molecular Biology
Background:
- Diffuse large B-cell lymphoma (DLBCL) is the most prevalent adult B-cell lymphoma.
- CDGSH iron sulfur domain 2 (CISD2) is an iron-sulfur protein crucial for cell proliferation, with aberrant expression linked to various cancers.
- The specific role of CISD2 in DLBCL pathogenesis and prognosis remained largely undetermined.
Purpose of the Study:
- To investigate the expression levels of CISD2 in DLBCL.
- To evaluate the prognostic significance of CISD2 and its related genes in DLBCL.
- To develop a predictive model for DLBCL prognosis and immune infiltration.
Main Methods:
- Differential expression analysis of CISD2 using public databases, qRT-PCR, and Western blot.
- Prognostic impact assessment via Kaplan-Meier plotter and drug sensitivity analysis using CellMiner.
- Development of a 27-gene risk signature (CISD2Risk) using LASSO Cox regression, followed by nomogram construction and immune infiltration analysis (ESTIMATE, CIBERSORT, MCP-counter).
Main Results:
- CISD2 was significantly upregulated in DLBCL tissues and cell lines, correlating with poor prognosis across multiple datasets.
- A 27-gene CISD2Risk signature was established, demonstrating association with poorer prognosis and therapeutic response.
- High CISD2Risk correlated with increased stromal and immune scores but was negatively associated with key immune infiltrating cells, indicating its role in the tumor microenvironment.
Conclusions:
- Elevated CISD2 expression is a marker of poor prognosis in DLBCL.
- The validated CISD2Risk model offers a robust tool for prognostic prediction and treatment monitoring in DLBCL.
- CISD2Risk serves as a potential indicator of immune infiltration and aids in clinical decision-making for DLBCL patients.
Background:
Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell lymphoma in adults. CDGSH iron sulfur domain 2 (CISD2) is an iron-sulfur protein and plays a critical role of cell proliferation. The aberrant expression of CISD2 is associated with the progression of multiple cancers. However, its role in DLBCL remains unclear.
Methods:
The differential expression of CISD2 was identified via public databases, and quantitative real-time PCR (qRT-PCR) and western blot were used to identifed the expression of CISD2. We estimated the impact of CISD2 on clinical prognosis using the Kaplan-Meier plotter. Meanwhile, the drug sensitivity of CISD2 was assessed using CellMiner database. The 100 CISD2-related genes from STRING obtained and analyzed using the LASSO Cox regression. A CISD2 related signature for risk model (CISD2Risk) was established. The PPI network of CISD2Risk was performed, and functional enrichment was conducted through the DAVID database. The impacts of CISD2Risk on clinical features were analyzed. ESTIMATE, CIBERSORT, and MCP-counter algorithm were used to identify CISD2Risk associated with immune infiltration. Subsequently, Univariate and multivariate Cox regression analysis were applied, and a prognostic nomogram, accompanied by a calibration curve, was constructed to predict 1-, 3-, and 5-years survival probabilities.
Results:
CISD2 was upregulated in DLBCL patients comparing with normal controls via public datasets, similarly, CISD2 was highly expressed in DLBCL cell lines. Overexpression of CISD2 was associated with poor prognosis in DLBCL patients based on the GSE31312, the GSE32918, and GSE93984 datasets (P<0.05). Nine drugs was considered as a potential therapeutic agents for CISD2. By using the LASSO cox regression, twenty seven genes were identified to construct CISD2Risk, and biological functions of these genes might be involved in apoptosis and P53 signaling pathway. The high CISD2Risk value had a worse prognosis and therapeutic effect (P<0.05). The higher stromal score, immune score, and ESTIMATE score were associated with lowe CISD2Risk value, CISD2Risk was negatively correlated with several immune infiltrating cells (macrophages M0 and M1, CD8 T cells, CD4 naïve T cells, NK cell, etc) that might be correlated with better prognosis. Additionally, The high CISD2Risk was identified as an independent prognostic factor for DLBCL patients using both univariate and multivariate Cox regression. The nomogram produced accurate predictions and the calibration curves were in good agreement.
Conclusion:
Our study demonstrates that high expression of CISD2 in DLBCL patients is associated with poor prognosis. We have successfully constructed and validated a good prognostic prediction and efficacy monitoring for CISD2Risk that included 27 genes. Meanwhile, CISD2Risk may be a promising evaluator for immune infiltration and serve as a reference for clinical decision-making in DLBCL patients.
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