Comprehensive analysis of the prognostic implication and immune infiltration of CISD2 in diffuse large B-cell lymphoma
BackgroundDiffuse 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...
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1277695/full |
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| author | ChaoFeng Zhang ChaoFeng Zhang ChaoFeng Zhang Qi Lin ChunTuan Li Yang Qiu JingYu Chen XiongPeng Zhu |
| author_facet | ChaoFeng Zhang ChaoFeng Zhang ChaoFeng Zhang Qi Lin ChunTuan Li Yang Qiu JingYu Chen XiongPeng Zhu |
| author_sort | ChaoFeng Zhang |
| collection | DOAJ |
| description | BackgroundDiffuse 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.MethodsThe 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.ResultsCISD2 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.ConclusionOur 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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| language | English |
| last_indexed | 2024-03-09T00:02:46Z |
| publishDate | 2023-12-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-33436622716b43749197108d8282e2d52023-12-12T15:01:06ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-12-011410.3389/fimmu.2023.12776951277695Comprehensive analysis of the prognostic implication and immune infiltration of CISD2 in diffuse large B-cell lymphomaChaoFeng Zhang0ChaoFeng Zhang1ChaoFeng Zhang2Qi Lin3ChunTuan Li4Yang Qiu5JingYu Chen6XiongPeng Zhu7Department of Haematology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, ChinaDepartment of Hematology and Rheumatology, The Affiliated Hospital of Putian University, Putian, ChinaThe School of Basic Medicine, Putian University, Putian, ChinaDepartment of Pharmacy, The Affiliated Hospital of Putian University, Putian, ChinaDepartment of Haematology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, ChinaThe School of Basic Medicine, Putian University, Putian, ChinaThe School of Basic Medicine, Putian University, Putian, ChinaDepartment of Haematology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, ChinaBackgroundDiffuse 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.MethodsThe 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.ResultsCISD2 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.ConclusionOur 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1277695/fulldiffuse large B cell lymphomaCISD2prognosisimmune infiltrationrisk model |
| spellingShingle | ChaoFeng Zhang ChaoFeng Zhang ChaoFeng Zhang Qi Lin ChunTuan Li Yang Qiu JingYu Chen XiongPeng Zhu Comprehensive analysis of the prognostic implication and immune infiltration of CISD2 in diffuse large B-cell lymphoma Frontiers in Immunology diffuse large B cell lymphoma CISD2 prognosis immune infiltration risk model |
| title | Comprehensive analysis of the prognostic implication and immune infiltration of CISD2 in diffuse large B-cell lymphoma |
| title_full | Comprehensive analysis of the prognostic implication and immune infiltration of CISD2 in diffuse large B-cell lymphoma |
| title_fullStr | Comprehensive analysis of the prognostic implication and immune infiltration of CISD2 in diffuse large B-cell lymphoma |
| title_full_unstemmed | Comprehensive analysis of the prognostic implication and immune infiltration of CISD2 in diffuse large B-cell lymphoma |
| title_short | Comprehensive analysis of the prognostic implication and immune infiltration of CISD2 in diffuse large B-cell lymphoma |
| title_sort | comprehensive analysis of the prognostic implication and immune infiltration of cisd2 in diffuse large b cell lymphoma |
| topic | diffuse large B cell lymphoma CISD2 prognosis immune infiltration risk model |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1277695/full |
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