Molecular classification and construction of the risk signature for diffuse large B-cell lymphoma based on vitamin B6 metabolism

Abstract Background and objectives Diffuse large B-cell lymphoma (DLBCL), characterized by high heterogeneity, shows significant differences in treatment responses and prognosis among patients. The underlying mechanisms of vitamin B6 metabolism in DLBCL remain unclear. This study aims to explore vit...

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Main Authors: Wen Wei, Dao Xin, Huawei Weng, Le Yu, Lingxi Jiang, Yuxin Man
Format: Article
Language:English
Published: Springer 2025-07-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-03122-w
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author Wen Wei
Dao Xin
Huawei Weng
Le Yu
Lingxi Jiang
Yuxin Man
author_facet Wen Wei
Dao Xin
Huawei Weng
Le Yu
Lingxi Jiang
Yuxin Man
author_sort Wen Wei
collection DOAJ
description Abstract Background and objectives Diffuse large B-cell lymphoma (DLBCL), characterized by high heterogeneity, shows significant differences in treatment responses and prognosis among patients. The underlying mechanisms of vitamin B6 metabolism in DLBCL remain unclear. This study aims to explore vitamin B6 metabolism characteristics, identify novel DLBCL molecular subtypes, and establish a predictive signature for prognosis. Methods We first conducted Mendelian randomization (MR) analysis to investigate the genetic association between the vitamin B6 metabolism gene and lymphoma. Subsequently, we utilized weighted gene co-expression network analysis (WGCNA) to identify vitamin B6 metabolism-related genes in DLBCL, combined with non-negative matrix factorization (NMF) to distinguish different molecular subtypes. On this basis, we constructed a risk signature using univariate Cox regression, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression. External validation of the signature was performed. Finally, we integrated clinical features to establish a nomogram to predict survival probabilities precisely. Results The vitamin B6 metabolism gene PSAT1 may play a protective role in lymphoma. Based on vitamin B6 metabolism features, we successfully identified four distinct DLBCL molecular subtypes. The constructed risk signature effectively assessed patients’ risk status and combined clinical features to establish a nomogram. This signature can precisely predict 1-year, 3-year, and 5-year survival probabilities for DLBCL patients, providing essential references for individualized management. Conclusion This study identified novel DLBCL molecular subtypes based on vitamin B6 metabolism characteristics and established a risk signature with clinical application value. These findings provide a new direction for the precise management of DLBCL patients.
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spelling doaj-art-829f2debd77d4af7ad4e237e765b2cfd2025-08-20T03:46:09ZengSpringerDiscover Oncology2730-60112025-07-0116111810.1007/s12672-025-03122-wMolecular classification and construction of the risk signature for diffuse large B-cell lymphoma based on vitamin B6 metabolismWen Wei0Dao Xin1Huawei Weng2Le Yu3Lingxi Jiang4Yuxin Man5Department of Medical Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of ChinaDepartment of Oncology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Medical Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of ChinaDepartment of Medical Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of ChinaSichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, University of Electronic Science and TechnologyDepartment of Medical Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of ChinaAbstract Background and objectives Diffuse large B-cell lymphoma (DLBCL), characterized by high heterogeneity, shows significant differences in treatment responses and prognosis among patients. The underlying mechanisms of vitamin B6 metabolism in DLBCL remain unclear. This study aims to explore vitamin B6 metabolism characteristics, identify novel DLBCL molecular subtypes, and establish a predictive signature for prognosis. Methods We first conducted Mendelian randomization (MR) analysis to investigate the genetic association between the vitamin B6 metabolism gene and lymphoma. Subsequently, we utilized weighted gene co-expression network analysis (WGCNA) to identify vitamin B6 metabolism-related genes in DLBCL, combined with non-negative matrix factorization (NMF) to distinguish different molecular subtypes. On this basis, we constructed a risk signature using univariate Cox regression, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression. External validation of the signature was performed. Finally, we integrated clinical features to establish a nomogram to predict survival probabilities precisely. Results The vitamin B6 metabolism gene PSAT1 may play a protective role in lymphoma. Based on vitamin B6 metabolism features, we successfully identified four distinct DLBCL molecular subtypes. The constructed risk signature effectively assessed patients’ risk status and combined clinical features to establish a nomogram. This signature can precisely predict 1-year, 3-year, and 5-year survival probabilities for DLBCL patients, providing essential references for individualized management. Conclusion This study identified novel DLBCL molecular subtypes based on vitamin B6 metabolism characteristics and established a risk signature with clinical application value. These findings provide a new direction for the precise management of DLBCL patients.https://doi.org/10.1007/s12672-025-03122-wDiffuse large B-cell lymphomaVitamin B6 metabolismMolecular subtypePrognosisSignature
spellingShingle Wen Wei
Dao Xin
Huawei Weng
Le Yu
Lingxi Jiang
Yuxin Man
Molecular classification and construction of the risk signature for diffuse large B-cell lymphoma based on vitamin B6 metabolism
Discover Oncology
Diffuse large B-cell lymphoma
Vitamin B6 metabolism
Molecular subtype
Prognosis
Signature
title Molecular classification and construction of the risk signature for diffuse large B-cell lymphoma based on vitamin B6 metabolism
title_full Molecular classification and construction of the risk signature for diffuse large B-cell lymphoma based on vitamin B6 metabolism
title_fullStr Molecular classification and construction of the risk signature for diffuse large B-cell lymphoma based on vitamin B6 metabolism
title_full_unstemmed Molecular classification and construction of the risk signature for diffuse large B-cell lymphoma based on vitamin B6 metabolism
title_short Molecular classification and construction of the risk signature for diffuse large B-cell lymphoma based on vitamin B6 metabolism
title_sort molecular classification and construction of the risk signature for diffuse large b cell lymphoma based on vitamin b6 metabolism
topic Diffuse large B-cell lymphoma
Vitamin B6 metabolism
Molecular subtype
Prognosis
Signature
url https://doi.org/10.1007/s12672-025-03122-w
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