CHN1 is a Novel Prognostic Marker for Diffuse Large B-Cell Lymphoma

Sun, Jie; Zhu, Xiaoquan; Zhao, Yanyang; Zhou, Qi; Qi, Ruomei; Liu, Hui

doi:10.2147/pgpm.s301718

Cited by 3 publications

(3 citation statements)

References 54 publications

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“…B cells as immunomodulatory cells, positive mediators, and antigen-presenting cells play a role in modulating the immune response to cancer ( 83 ). We found that DLBCL with high CISD2Risk value exhibited increased B cell infiltrations in accord with several studies ( 47 , 77 , 84 , 85 ). B cells are part of the adaptive immune system and can produce antibodies against cancer cells.…”

Section: Discussionsupporting

confidence: 92%

Comprehensive analysis of the prognostic implication and immune infiltration of CISD2 in diffuse large B-cell lymphoma

Zhang,

Lin,

et al. 2023

Front. Immunol.

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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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Section: Discussionsupporting

confidence: 92%

Comprehensive analysis of the prognostic implication and immune infiltration of CISD2 in diffuse large B-cell lymphoma

Zhang,

Lin,

et al. 2023

Front. Immunol.

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“…LAT gene encodes linker for activation of T-cells, playing a key role in activation of T-cell signaling pathways following activation of the TCR signal transduction pathway [ 36 ]. In human DLBCL, high expression levels of LAT were associated with prolonged prognosis [ 37 ]. On the other hand, these genes were up-regulated in R-group in this study, which appears to be contradictory to the results in previous studies.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiles associated with early relapse during first remission induction in canine multicentric high-grade B-cell lymphoma

TOYODA,

TANI,

GOTO-KOSHINO

et al. 2024

The Journal of Veterinary Medical Science

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Although chemotherapy using CHOP-based protocol induces remission in most cases of canine multicentric high-grade B-cell lymphoma (mhBCL), some cases develop early relapse during the first induction protocol. In this study, we examined the gene expression profiles of canine mhBCL before chemotherapy and investigated their associations with early relapse during the first whole CHOP-based protocol. Twenty-five cases of mhBCL treated with CHOP-based protocol as first induction chemotherapy were included in this study. Sixteen cases completed the first whole CHOP-based protocol without relapse (S-group), and nine developed relapse during the chemotherapy (R-group). RNA-seq was performed on samples from neoplastic lymph nodes. Differentially expressed genes (DEGs) were extracted by the comparison of gene expression profiles between S- and R-groups, and the differences in the expression levels of these genes were validated by RT-qPCR. Extracted 179 DEGs included the genes related to chemokine CC motif ligand, T-cell receptor signaling pathway, and PD-L1 expression and PD-1 checkpoint pathway. We focused on chemokine CC motif ligand, and CCL4 was confirmed to be significantly downregulated in the R-group ( P =0.039). We also focused on the genes related to T-cell signaling pathway, and CD3E ( P =0.039), ITK ( P =0.023), and LAT ( P =0.023) genes were confirmed to be significantly upregulated in the R-group. The current results suggest that both changes in tumor cells and the interactions between tumor cells and immune cells are associated with the efficacy of the chemotherapy for first remission induction.

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“…However, limited information on CHN1 has been reported in relation to cancer. Couch et al showed that CHN1 could be used as a biomarker for the diagnosis of esophageal squamous dysplasia and squamous cell cancer [ 27 ]; Sun et al, however, claimed that CHN1 could be used as a novel prognostic marker for diffuse large B-cell lymphoma [ 28 ]. Previously, Liu et al showed that CHN1 was highly expressed in human cervical cancer tissues and was positively regulated by miR-205 ; furthermore, high expression of CHN1 was also correlated with lymph node metastasis [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

CHN1 promotes epithelial–mesenchymal transition via the Akt/GSK-3β/Snail pathway in cervical carcinoma

Zhao

Wang

et al. 2021

J Transl Med

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Background Metastasis and invasion are crucial in determining the mortality of cervical carcinoma (CC) patients. The epithelial–mesenchymal transition (EMT) is now a universal explanation for the mechanisms of tumor metastasis. Α-chimeric protein (α-chimaerin, CHN1) plays an important role in the regulation of signal transduction and development. However, the molecular regulatory relationships between CHN1 and CC progression in relation to EMT have not yet been identified. Methods The expression of CHN1 in CC tissues, adjacent tissues, and lymph node metastases from CC patients was detected by immunohistochemistry. Upregulation and knockdown of CHN1 were achieved by transfection of CC cells. The effect of CHN1 on cell proliferation was determined by CCK-8 and plate clone formation assays. Changes in migration and invasion capabilities were evaluated using scratch migration and transwell invasion assays. The effect of CHN1 overexpression and interference on xenograft tumor growth was determined by tumor weight and pathological analyses. The expression of EMT-related mRNAs was measured by qRT-PCR in transfected CC cells. EMT-related proteins and Akt/GSK-3β/Snail signaling pathway-related proteins were also evaluated by western blotting. Results CHN1 was overexpressed in CC tissues and was associated with lymph node metastasis and low survival in CC patients. Overexpression of CHN1 promoted cell proliferation, migration, and invasion in CC cells. In contrast, silencing of CHN1 inhibited these phenomena. Overexpression of CHN1 promoted tumor formation in an in vivo xenograft tumor mouse model, with increased tumor volumes and weights. In addition, CHN1 induced the expression of EMT-related transcription factors, accompanied by the decreased expression of epithelial markers and increased expression of mesenchymal markers. The Akt/GSK-3β/Snail signaling pathway was activated by overexpression of CHN1 in vitro, and activation of this pathway was inhibited by the signaling pathway inhibitor LY294002. Conclusion These results suggest that CHN1 promotes the development and progression of cervical carcinoma via the Akt/GSK-3β/Snail pathway by inducing EMT.

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CHN1 is a Novel Prognostic Marker for Diffuse Large B-Cell Lymphoma

Cited by 3 publications

References 54 publications

Comprehensive analysis of the prognostic implication and immune infiltration of CISD2 in diffuse large B-cell lymphoma

Comprehensive analysis of the prognostic implication and immune infiltration of CISD2 in diffuse large B-cell lymphoma

Gene expression profiles associated with early relapse during first remission induction in canine multicentric high-grade B-cell lymphoma

CHN1 promotes epithelial–mesenchymal transition via the Akt/GSK-3β/Snail pathway in cervical carcinoma

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