Dataset Information

Development and validation of a combined cuproptosis and immunogenic cell death prognostic model for diffuse large B-cell lymphoma.

ABSTRACT:

Background

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma worldwide with a high degree of heterogeneity. Cuproptosis and immunogenic cell death (ICD) have been considered to be vital for tumor progression. However, current understanding of cuproptosis and immunogenic cell death in DLBCL is still very limited. We aim to explore a prognostic model combining cuproptosis and immunogenic cell death in DLBCL.

Methods

Pearson's correlation analysis was utilized to acquire lncRNAs associated with cuproptosis and immunogenic cell death. Prognostic biomarker identification and model construction involved the use of univariate Cox regression, least absolute shrinkage and selection operator (LASSO) Cox regression, and multivariate Cox regression. We assessed the predictive capability of the risk model by conducting Kaplan-Meier analysis and time-dependent ROC analysis. The analysis and comparison of immune infiltration and drug sensitivity were conducted in this study. Moreover, RT-qPCR was employed to validate the expression of lncRNAs associated with cuproptosis and immunogenic cell death in DLBCL cell lines.

Results

We identified 4 prognosis-related lncRNAs (ANKRD10-IT1, HOXB-AS1, LINC00520 and LINC01165) that were correlated with cuproptosis and immunogenic cell death. The model was verified to have a good and independent predictive ability in the prognostic prediction of DLBCL patients. Moreover, significant difference was observed in immune infiltration and drug sensitivity between high- and low-risk groups.

Conclusion

Our discoveries could enhance the comprehension of the role of cuproptosis and ICD in DLBCL, potentially offering novel viewpoints and knowledge for personalized and precise treatment of DLBCL individuals.

SUBMITTER: Wang N

PROVIDER: S-EPMC10866411 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

Development and validation of a combined cuproptosis and immunogenic cell death prognostic model for diffuse large B-cell lymphoma.

Wang Nana N Shi Shanshan S Li Moran M Yu Xiaoning X Ma Guangxin G

Aging 20240126 2

<h4>Background</h4>Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma worldwide with a high degree of heterogeneity. Cuproptosis and immunogenic cell death (ICD) have been considered to be vital for tumor progression. However, current understanding of cuproptosis and immunogenic cell death in DLBCL is still very limited. We aim to explore a prognostic model combining cuproptosis and immunogenic cell death in DLBCL.<h4>Methods</h4>Pearson's correlation analysis ...[more]

PMID: 38284893

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Project description:Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous disease. Therefore, more reliable biomarkers are required to better predict the prognosis of DLBCL. Cuproptosis is a novel identified form of programmed cell death (PCD) that is different from oxidative stress-related cell death (e.g., apoptosis, ferroptosis, and necroptosis) by Tsvetkov and colleagues in a recent study released in Science. Cuproptosis is copper-dependent PCD that is closely tied to mitochondrial metabolism. However, the prognostic value of cuproptosis-related genes (CRGs) in DLBCL remains to be further elucidated. In the present study, we systematically evaluated the molecular changes of CRGs in DLBCL and found them to be associated with prognosis. Subsequently, based on the expression profiles of CRGs, we characterized the heterogeneity of DLBCL by identifying two distinct subtypes using consensus clustering. Two isoforms exhibited different survival, biological functions, chemotherapeutic drug sensitivity, and immune microenvironment. After identifying differentially expressed genes (DEGs) between CRG clusters, we built a prognostic model with the Least absolute shrinkage and selection operator (LASSO) Cox regression analysis and validated its prognostic value by Cox regression analysis, Kaplan-Meier curves, and receiver operating characteristic (ROC) curves. In addition, the risk score can predict clinical characteristics, levels of immune cell infiltration, and prognosis. Furthermore, a nomogram incorporating clinical features and risk score was generated to optimize risk stratification and quantify risk assessment. Compared to the International Prognostic Index (IPI), the nomogram has demonstrated more accuracy in survival prediction. Furthermore, we validated the prognostic gene expression levels through external experiments. In conclusion, cuproptosis-related gene signature can serve as a potential prognostic predictor in DLBCL patients and may provide new insights into cancer therapeutic targets.

Project description:BackgroundDiffuse large B-cell lymphoma (DLBCL) is a heterogeneous group with varied pathophysiological, genetic, and clinical features, accounting for approximately one-third of all lymphoma cases worldwide. Notwithstanding that unprecedented scientific progress has been achieved over the years, the survival of DLBCL patients remains low, emphasizing the need to develop novel prognostic biomarkers for early risk stratification and treatment optimization.MethodIn this study, we screened genes related to the overall survival (OS) of DLBCL patients in datasets GSE117556, GSE10846, and GSE31312 using univariate Cox analysis. Survival-related genes among the three datasets were screened according to the criteria: hazard ratio (HR) >1 or <1 and p-value <0.01. Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate Cox regression analysis were used to optimize and establish the final gene risk prediction model. The TCGA-NCICCR datasets and our clinical cohort were used to validate the performance of the prediction model. CIBERSORT and ssGSEA algorithms were used to estimate immune scores in the high- and low-risk groups.ResultsWe constructed an eight-gene prognostic signature that could reliably predict the clinical outcome in training, testing, and validation cohorts. Our prognostic signature also performed distinguished areas under the ROC curve in each dataset, respectively. After stratification based on clinical characteristics such as cell-of-origin (COO), age, eastern cooperative oncology group (ECOG) performance status, international prognostic index (IPI), stage, and MYC/BCL2 expression, the difference in OS between the high- and low-risk groups was statistically significant. Next, univariate and multivariate analyses revealed that the risk score model had a significant prediction value. Finally, a nomogram was established to visualize the prediction model. Of note, we found that the low-risk group was enriched with immune cells.ConclusionIn summary, we identified an eight-gene prognostic prediction model that can effectively predict survival outcomes of patients with DLBCL and built a nomogram to visualize the perdition model. We also explored immune alterations between high- and low-risk groups.

Dataset Information

Development and validation of a combined cuproptosis and immunogenic cell death prognostic model for diffuse large B-cell lymphoma.

Background

Methods

Results

Conclusion

Publications

Development and validation of a combined cuproptosis and immunogenic cell death prognostic model for diffuse large B-cell lymphoma.

Similar Datasets

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