Cargando…
Identifying a novel ferroptosis-related prognostic score for predicting prognosis in chronic lymphocytic leukemia
BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western world. Although the treatment landscape for CLL is rapidly evolving, there are still some patients who develop drug resistance or disease refractory. Ferroptosis is a type of lipid peroxidation–induced cell dea...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9582233/ https://www.ncbi.nlm.nih.gov/pubmed/36275721 http://dx.doi.org/10.3389/fimmu.2022.962000 |
_version_ | 1784812785359650816 |
---|---|
author | Pan, Bihui Li, Yue Xu, Zhangdi Miao, Yi Yin, Hua Kong, Yilin Zhang, Xinyu Liang, Jinhua Xia, Yi Wang, Li Li, Jianyong Wu, Jiazhu Xu, Wei |
author_facet | Pan, Bihui Li, Yue Xu, Zhangdi Miao, Yi Yin, Hua Kong, Yilin Zhang, Xinyu Liang, Jinhua Xia, Yi Wang, Li Li, Jianyong Wu, Jiazhu Xu, Wei |
author_sort | Pan, Bihui |
collection | PubMed |
description | BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western world. Although the treatment landscape for CLL is rapidly evolving, there are still some patients who develop drug resistance or disease refractory. Ferroptosis is a type of lipid peroxidation–induced cell death and has been suggested to have prognostic value in several cancers. Our research aims to build a prognostic model to improve risk stratification in CLL patients and facilitate more accurate assessment for clinical management. METHODS: The differentially expressed ferroptosis-related genes (FRGs) in CLL were filtered through univariate Cox regression analysis based on public databases. Least absolute shrinkage and selection operator (LASSO) Cox algorithms were performed to construct a prognostic risk model. CIBERSORT and single-sample gene set enrichment analysis (ssGSEA) were performed to estimate the immune infiltration score and immune-related pathways. A total of 36 CLL patients in our center were enrolled in this study as a validation cohort. Moreover, a nomogram model was established to predict the prognosis. RESULTS: A total of 15 differentially expressed FRGs with prognostic significance were screened out. After minimizing the potential risk of overfitting, we constructed a novel ferroptosis-related prognostic score (FPS) model with nine FRGs (AKR1C3, BECN1, CAV1, CDKN2A, CXCL2, JDP2, SIRT1, SLC1A5, and SP1) and stratified patients into low- and high-risk groups. Kaplan–Meier analysis showed that patients with high FPS had worse overall survival (OS) (P<0.0001) and treatment-free survival (TFS) (P<0.0001). ROC curves evaluated the prognostic prediction ability of the FPS model. Additionally, the immune cell types and immune-related pathways were correlated with the risk scores in CLL patients. In the validation cohort, the results confirmed that the high-risk group was related to worse OS (P<0.0001), progress-free survival (PFS) (P=0.0140), and TFS (P=0.0072). In the multivariate analysis, only FPS (P=0.011) and CLL-IPI (P=0.010) were independent risk indicators for OS. Furthermore, we established a nomogram including FPS and CLL-IPI that could strongly and reliably predict individual prognosis. CONCLUSION: A novel FPS model can be used in CLL for prognostic prediction. The model index may also facilitate the development of new clinical ferroptosis-targeted therapies in patients with CLL. |
format | Online Article Text |
id | pubmed-9582233 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95822332022-10-21 Identifying a novel ferroptosis-related prognostic score for predicting prognosis in chronic lymphocytic leukemia Pan, Bihui Li, Yue Xu, Zhangdi Miao, Yi Yin, Hua Kong, Yilin Zhang, Xinyu Liang, Jinhua Xia, Yi Wang, Li Li, Jianyong Wu, Jiazhu Xu, Wei Front Immunol Immunology BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western world. Although the treatment landscape for CLL is rapidly evolving, there are still some patients who develop drug resistance or disease refractory. Ferroptosis is a type of lipid peroxidation–induced cell death and has been suggested to have prognostic value in several cancers. Our research aims to build a prognostic model to improve risk stratification in CLL patients and facilitate more accurate assessment for clinical management. METHODS: The differentially expressed ferroptosis-related genes (FRGs) in CLL were filtered through univariate Cox regression analysis based on public databases. Least absolute shrinkage and selection operator (LASSO) Cox algorithms were performed to construct a prognostic risk model. CIBERSORT and single-sample gene set enrichment analysis (ssGSEA) were performed to estimate the immune infiltration score and immune-related pathways. A total of 36 CLL patients in our center were enrolled in this study as a validation cohort. Moreover, a nomogram model was established to predict the prognosis. RESULTS: A total of 15 differentially expressed FRGs with prognostic significance were screened out. After minimizing the potential risk of overfitting, we constructed a novel ferroptosis-related prognostic score (FPS) model with nine FRGs (AKR1C3, BECN1, CAV1, CDKN2A, CXCL2, JDP2, SIRT1, SLC1A5, and SP1) and stratified patients into low- and high-risk groups. Kaplan–Meier analysis showed that patients with high FPS had worse overall survival (OS) (P<0.0001) and treatment-free survival (TFS) (P<0.0001). ROC curves evaluated the prognostic prediction ability of the FPS model. Additionally, the immune cell types and immune-related pathways were correlated with the risk scores in CLL patients. In the validation cohort, the results confirmed that the high-risk group was related to worse OS (P<0.0001), progress-free survival (PFS) (P=0.0140), and TFS (P=0.0072). In the multivariate analysis, only FPS (P=0.011) and CLL-IPI (P=0.010) were independent risk indicators for OS. Furthermore, we established a nomogram including FPS and CLL-IPI that could strongly and reliably predict individual prognosis. CONCLUSION: A novel FPS model can be used in CLL for prognostic prediction. The model index may also facilitate the development of new clinical ferroptosis-targeted therapies in patients with CLL. Frontiers Media S.A. 2022-10-06 /pmc/articles/PMC9582233/ /pubmed/36275721 http://dx.doi.org/10.3389/fimmu.2022.962000 Text en Copyright © 2022 Pan, Li, Xu, Miao, Yin, Kong, Zhang, Liang, Xia, Wang, Li, Wu and Xu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Pan, Bihui Li, Yue Xu, Zhangdi Miao, Yi Yin, Hua Kong, Yilin Zhang, Xinyu Liang, Jinhua Xia, Yi Wang, Li Li, Jianyong Wu, Jiazhu Xu, Wei Identifying a novel ferroptosis-related prognostic score for predicting prognosis in chronic lymphocytic leukemia |
title | Identifying a novel ferroptosis-related prognostic score for predicting prognosis in chronic lymphocytic leukemia |
title_full | Identifying a novel ferroptosis-related prognostic score for predicting prognosis in chronic lymphocytic leukemia |
title_fullStr | Identifying a novel ferroptosis-related prognostic score for predicting prognosis in chronic lymphocytic leukemia |
title_full_unstemmed | Identifying a novel ferroptosis-related prognostic score for predicting prognosis in chronic lymphocytic leukemia |
title_short | Identifying a novel ferroptosis-related prognostic score for predicting prognosis in chronic lymphocytic leukemia |
title_sort | identifying a novel ferroptosis-related prognostic score for predicting prognosis in chronic lymphocytic leukemia |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9582233/ https://www.ncbi.nlm.nih.gov/pubmed/36275721 http://dx.doi.org/10.3389/fimmu.2022.962000 |
work_keys_str_mv | AT panbihui identifyinganovelferroptosisrelatedprognosticscoreforpredictingprognosisinchroniclymphocyticleukemia AT liyue identifyinganovelferroptosisrelatedprognosticscoreforpredictingprognosisinchroniclymphocyticleukemia AT xuzhangdi identifyinganovelferroptosisrelatedprognosticscoreforpredictingprognosisinchroniclymphocyticleukemia AT miaoyi identifyinganovelferroptosisrelatedprognosticscoreforpredictingprognosisinchroniclymphocyticleukemia AT yinhua identifyinganovelferroptosisrelatedprognosticscoreforpredictingprognosisinchroniclymphocyticleukemia AT kongyilin identifyinganovelferroptosisrelatedprognosticscoreforpredictingprognosisinchroniclymphocyticleukemia AT zhangxinyu identifyinganovelferroptosisrelatedprognosticscoreforpredictingprognosisinchroniclymphocyticleukemia AT liangjinhua identifyinganovelferroptosisrelatedprognosticscoreforpredictingprognosisinchroniclymphocyticleukemia AT xiayi identifyinganovelferroptosisrelatedprognosticscoreforpredictingprognosisinchroniclymphocyticleukemia AT wangli identifyinganovelferroptosisrelatedprognosticscoreforpredictingprognosisinchroniclymphocyticleukemia AT lijianyong identifyinganovelferroptosisrelatedprognosticscoreforpredictingprognosisinchroniclymphocyticleukemia AT wujiazhu identifyinganovelferroptosisrelatedprognosticscoreforpredictingprognosisinchroniclymphocyticleukemia AT xuwei identifyinganovelferroptosisrelatedprognosticscoreforpredictingprognosisinchroniclymphocyticleukemia |