A Mitochondria‐Related Signature in Diffuse Large B‐Cell Lymphoma: Prognosis, Immune and Therapeutic Features
ABSTRACT Background Distinctive heterogeneity characterizes diffuse large B‐cell lymphoma (DLBCL), one of the most frequent types of non‐Hodgkin's lymphoma. Mitochondria have been demonstrated to be closely involved in tumorigenesis and progression, particularly in DLBCL. Objective The purposes...
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| Format: | Article |
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Wiley
2025-01-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.70602 |
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| author | Zhen‐Zhong Zhou Jia‐Chen Lu Song‐Bin Guo Xiao‐Peng Tian Hai‐Long Li Hui Zhou Wei‐Juan Huang |
| author_facet | Zhen‐Zhong Zhou Jia‐Chen Lu Song‐Bin Guo Xiao‐Peng Tian Hai‐Long Li Hui Zhou Wei‐Juan Huang |
| author_sort | Zhen‐Zhong Zhou |
| collection | DOAJ |
| description | ABSTRACT Background Distinctive heterogeneity characterizes diffuse large B‐cell lymphoma (DLBCL), one of the most frequent types of non‐Hodgkin's lymphoma. Mitochondria have been demonstrated to be closely involved in tumorigenesis and progression, particularly in DLBCL. Objective The purposes of this study were to identify the prognostic mitochondria‐related genes (MRGs) in DLBCL, and to develop a risk model based on MRGs and machine learning algorithms. Methods Transcriptome profiles and clinical information were obtained from the Gene Expression Omnibus (GEO) database. The risk model was defined using Least Absolute Shrinkage and Selection Operator (Lasso) regression algorithm, and its prognostic value was further examined in independent datasets. Patients were stratified into two clusters based on the risk scores, additionally a nomogram was generated based on the risk score and clinical characteristics. Gene pathway level, microenvironment, expression of targeted therapy‐associated genes, response to immunotherapy, drug sensitivity, and somatic mutation status were compared between clusters. Results Eighteen prognostic MRGs (DNM1L, PUSL1, CHCHD4, COX7A1, CPT1A, CYP27A1, POLDIP2, PCK2, MRPL2, PDK3, PDK4, MARC2, ACSM3, COA7, THNSL1, ATAD3B, C15orf48, TOMM70A) were identified to construct the risk model. Remarkable discrepancies were observed between groups. The high‐risk group had shorter overall survival, less immune infiltration, lower CD20 and higher PD‐L1 expression than the low‐risk group. Distinct immune microenvironment, responses to immunotherapy and predictive drug IC50 values were found between groups. Conclusions We established a novel prognostic mitochondria‐related signature by machine learning algorithm, which also demonstrated outstanding predictive value in tumor microenvironment and responses to therapies. |
| format | Article |
| id | doaj-art-bb207dc5211945a9be80dad59e25485c |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-bb207dc5211945a9be80dad59e25485c2025-01-24T08:46:07ZengWileyCancer Medicine2045-76342025-01-01142n/an/a10.1002/cam4.70602A Mitochondria‐Related Signature in Diffuse Large B‐Cell Lymphoma: Prognosis, Immune and Therapeutic FeaturesZhen‐Zhong Zhou0Jia‐Chen Lu1Song‐Bin Guo2Xiao‐Peng Tian3Hai‐Long Li4Hui Zhou5Wei‐Juan Huang6Department of Medical Oncology Sun Yat‐sen University Cancer Center Guangzhou ChinaDepartment of Medical Oncology Sun Yat‐sen University Cancer Center Guangzhou ChinaDepartment of Medical Oncology Sun Yat‐sen University Cancer Center Guangzhou ChinaDepartment of Medical Oncology Sun Yat‐sen University Cancer Center Guangzhou ChinaDepartment of Medical Oncology Sun Yat‐sen University Cancer Center Guangzhou ChinaDepartment of Respiratory Oncology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui ChinaDepartment of Pharmacology, College of Pharmacy Jinan University Guangzhou ChinaABSTRACT Background Distinctive heterogeneity characterizes diffuse large B‐cell lymphoma (DLBCL), one of the most frequent types of non‐Hodgkin's lymphoma. Mitochondria have been demonstrated to be closely involved in tumorigenesis and progression, particularly in DLBCL. Objective The purposes of this study were to identify the prognostic mitochondria‐related genes (MRGs) in DLBCL, and to develop a risk model based on MRGs and machine learning algorithms. Methods Transcriptome profiles and clinical information were obtained from the Gene Expression Omnibus (GEO) database. The risk model was defined using Least Absolute Shrinkage and Selection Operator (Lasso) regression algorithm, and its prognostic value was further examined in independent datasets. Patients were stratified into two clusters based on the risk scores, additionally a nomogram was generated based on the risk score and clinical characteristics. Gene pathway level, microenvironment, expression of targeted therapy‐associated genes, response to immunotherapy, drug sensitivity, and somatic mutation status were compared between clusters. Results Eighteen prognostic MRGs (DNM1L, PUSL1, CHCHD4, COX7A1, CPT1A, CYP27A1, POLDIP2, PCK2, MRPL2, PDK3, PDK4, MARC2, ACSM3, COA7, THNSL1, ATAD3B, C15orf48, TOMM70A) were identified to construct the risk model. Remarkable discrepancies were observed between groups. The high‐risk group had shorter overall survival, less immune infiltration, lower CD20 and higher PD‐L1 expression than the low‐risk group. Distinct immune microenvironment, responses to immunotherapy and predictive drug IC50 values were found between groups. Conclusions We established a novel prognostic mitochondria‐related signature by machine learning algorithm, which also demonstrated outstanding predictive value in tumor microenvironment and responses to therapies.https://doi.org/10.1002/cam4.70602diffuse large B‐cell lymphomadrug sensitivitygene set enrichment analysisimmune environmentmitochondria‐related genesprognostic model |
| spellingShingle | Zhen‐Zhong Zhou Jia‐Chen Lu Song‐Bin Guo Xiao‐Peng Tian Hai‐Long Li Hui Zhou Wei‐Juan Huang A Mitochondria‐Related Signature in Diffuse Large B‐Cell Lymphoma: Prognosis, Immune and Therapeutic Features Cancer Medicine diffuse large B‐cell lymphoma drug sensitivity gene set enrichment analysis immune environment mitochondria‐related genes prognostic model |
| title | A Mitochondria‐Related Signature in Diffuse Large B‐Cell Lymphoma: Prognosis, Immune and Therapeutic Features |
| title_full | A Mitochondria‐Related Signature in Diffuse Large B‐Cell Lymphoma: Prognosis, Immune and Therapeutic Features |
| title_fullStr | A Mitochondria‐Related Signature in Diffuse Large B‐Cell Lymphoma: Prognosis, Immune and Therapeutic Features |
| title_full_unstemmed | A Mitochondria‐Related Signature in Diffuse Large B‐Cell Lymphoma: Prognosis, Immune and Therapeutic Features |
| title_short | A Mitochondria‐Related Signature in Diffuse Large B‐Cell Lymphoma: Prognosis, Immune and Therapeutic Features |
| title_sort | mitochondria related signature in diffuse large b cell lymphoma prognosis immune and therapeutic features |
| topic | diffuse large B‐cell lymphoma drug sensitivity gene set enrichment analysis immune environment mitochondria‐related genes prognostic model |
| url | https://doi.org/10.1002/cam4.70602 |
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