Identification and Development of a 4-Gene Ferroptosis Signature Predicting Overall Survival for Diffuse Large B-Cell Lymphoma
Background: Diffuse large B-cell lymphoma (DLBCL) is a well-differentiated disease, which makes the diagnosis and therapeutic strategy a difficult problem. While ferroptosis, as an iron-dependent form of regulated cell death, it plays an important role in causing several types of cancer. This study...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2023-02-01
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| Series: | Technology in Cancer Research & Treatment |
| Online Access: | https://doi.org/10.1177/15330338221147772 |
| _version_ | 1828036047506767872 |
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| author | Huitao Wu MS Junyan Zhang MS Li Fu PhD Rilige Wu MS Zhenyang Gu PhD Chengliang Yin PhD Kunlun He PhD |
| author_facet | Huitao Wu MS Junyan Zhang MS Li Fu PhD Rilige Wu MS Zhenyang Gu PhD Chengliang Yin PhD Kunlun He PhD |
| author_sort | Huitao Wu MS |
| collection | DOAJ |
| description | Background: Diffuse large B-cell lymphoma (DLBCL) is a well-differentiated disease, which makes the diagnosis and therapeutic strategy a difficult problem. While ferroptosis, as an iron-dependent form of regulated cell death, it plays an important role in causing several types of cancer. This study is aimed at exploring the prognostic value of ferroptosis-related genes in DLBCL. Methods: In our study, mRNA expression and matching clinical data of DLBCL patients were derived from Gene Expression Omnibus (GEO) database. First, multivariate cox regression model and nomogram which can predict the DLBCL patients’ prognosis were built and validated. The multigene signature was constructed and optimized by the least absolute shrinkage and selection operator (LASSO) cox regression model. Also, ferroptosis-related subtypes were developed by consistent cluster. Last but not least, we explored the association between categories of infiltrating immune cells and model genes’ expression. Results: Our results showed that 27 gene expressions were correlated with overall survival (OS) in the univariate cox regression analysis. A 4-gene signature was constructed through these genes to stratify patients into high-low risk groups using risk score derived from model (model 1:gene expression model). The OS of patients in the high-risk group was shorter than that of patients in the low-risk group in the TNM stage and clinically distinct subtypes (activated B cell [ABC], germinal center B cell [GCB]) ( P < .001). Furthermore, it was shown that the risk score was an independent factor in clinical cox regression model for OS (model 2:clinical model) (HR>1, P < .010). Besides, in consistent cluster analysis, ferroptosis prognosis status was different among 3 subtypes. Moreover, the correlation analysis between 4-gene with immune cells showed dendritic cells may be significantly associated with DLBCL. Conclusion: This research constructed an innovative ferroptosis-related gene signature for prognostic estimation of DLBCL patients. Solutions targeting ferroptosis could be an important therapeutic intervention for DLBCL. |
| first_indexed | 2024-04-10T15:54:25Z |
| format | Article |
| id | doaj.art-f0fda497356a470b977d12a59767c935 |
| institution | Directory Open Access Journal |
| issn | 1533-0338 |
| language | English |
| last_indexed | 2024-04-10T15:54:25Z |
| publishDate | 2023-02-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Technology in Cancer Research & Treatment |
| spelling | doaj.art-f0fda497356a470b977d12a59767c9352023-02-10T18:33:19ZengSAGE PublishingTechnology in Cancer Research & Treatment1533-03382023-02-012210.1177/15330338221147772Identification and Development of a 4-Gene Ferroptosis Signature Predicting Overall Survival for Diffuse Large B-Cell LymphomaHuitao Wu MS0Junyan Zhang MS1Li Fu PhD2Rilige Wu MS3Zhenyang Gu PhD4Chengliang Yin PhD5Kunlun He PhD6 Intelligent Healthcare Team, Baidu Inc., Beijing, China National Engineering Laboratory for Medical Big Data Application Technology, , Beijing, China Key Laboratory of Novel Materials for Sensor of Zhejiang Province, College of Materials and Environmental Engineering, , Hangzhou, China National Engineering Laboratory for Medical Big Data Application Technology, , Beijing, China The Fifth Medical Center of PLA General Hospital, Beijing, China National Engineering Laboratory for Medical Big Data Application Technology, , Beijing, China Key Laboratory of Biomedical Engineering and Translational Medicine, Ministry of Industry and Information Technology, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, ChinaBackground: Diffuse large B-cell lymphoma (DLBCL) is a well-differentiated disease, which makes the diagnosis and therapeutic strategy a difficult problem. While ferroptosis, as an iron-dependent form of regulated cell death, it plays an important role in causing several types of cancer. This study is aimed at exploring the prognostic value of ferroptosis-related genes in DLBCL. Methods: In our study, mRNA expression and matching clinical data of DLBCL patients were derived from Gene Expression Omnibus (GEO) database. First, multivariate cox regression model and nomogram which can predict the DLBCL patients’ prognosis were built and validated. The multigene signature was constructed and optimized by the least absolute shrinkage and selection operator (LASSO) cox regression model. Also, ferroptosis-related subtypes were developed by consistent cluster. Last but not least, we explored the association between categories of infiltrating immune cells and model genes’ expression. Results: Our results showed that 27 gene expressions were correlated with overall survival (OS) in the univariate cox regression analysis. A 4-gene signature was constructed through these genes to stratify patients into high-low risk groups using risk score derived from model (model 1:gene expression model). The OS of patients in the high-risk group was shorter than that of patients in the low-risk group in the TNM stage and clinically distinct subtypes (activated B cell [ABC], germinal center B cell [GCB]) ( P < .001). Furthermore, it was shown that the risk score was an independent factor in clinical cox regression model for OS (model 2:clinical model) (HR>1, P < .010). Besides, in consistent cluster analysis, ferroptosis prognosis status was different among 3 subtypes. Moreover, the correlation analysis between 4-gene with immune cells showed dendritic cells may be significantly associated with DLBCL. Conclusion: This research constructed an innovative ferroptosis-related gene signature for prognostic estimation of DLBCL patients. Solutions targeting ferroptosis could be an important therapeutic intervention for DLBCL.https://doi.org/10.1177/15330338221147772 |
| spellingShingle | Huitao Wu MS Junyan Zhang MS Li Fu PhD Rilige Wu MS Zhenyang Gu PhD Chengliang Yin PhD Kunlun He PhD Identification and Development of a 4-Gene Ferroptosis Signature Predicting Overall Survival for Diffuse Large B-Cell Lymphoma Technology in Cancer Research & Treatment |
| title | Identification and Development of a 4-Gene Ferroptosis Signature Predicting Overall Survival for Diffuse Large B-Cell Lymphoma |
| title_full | Identification and Development of a 4-Gene Ferroptosis Signature Predicting Overall Survival for Diffuse Large B-Cell Lymphoma |
| title_fullStr | Identification and Development of a 4-Gene Ferroptosis Signature Predicting Overall Survival for Diffuse Large B-Cell Lymphoma |
| title_full_unstemmed | Identification and Development of a 4-Gene Ferroptosis Signature Predicting Overall Survival for Diffuse Large B-Cell Lymphoma |
| title_short | Identification and Development of a 4-Gene Ferroptosis Signature Predicting Overall Survival for Diffuse Large B-Cell Lymphoma |
| title_sort | identification and development of a 4 gene ferroptosis signature predicting overall survival for diffuse large b cell lymphoma |
| url | https://doi.org/10.1177/15330338221147772 |
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