Wei Wen, Xin Dao, Weng Huawei, Yu Le, Jiang Lingxi, Man Yuxin
Department of Medical Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, China.
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Discov Oncol. 2025 Jul 11;16(1):1314. doi: 10.1007/s12672-025-03122-w.
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.
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.
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.
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.
弥漫性大B细胞淋巴瘤（DLBCL）具有高度异质性，患者的治疗反应和预后存在显著差异。DLBCL中维生素B6代谢的潜在机制尚不清楚。本研究旨在探索维生素B6代谢特征，识别新的DLBCL分子亚型，并建立预后预测特征。
我们首先进行孟德尔随机化（MR）分析，以研究维生素B6代谢基因与淋巴瘤之间的遗传关联。随后，我们利用加权基因共表达网络分析（WGCNA）来识别DLBCL中与维生素B6代谢相关的基因，并结合非负矩阵分解（NMF）来区分不同的分子亚型。在此基础上，我们使用单变量Cox回归、最小绝对收缩和选择算子（LASSO）以及多变量Cox回归构建了一个风险特征。对该特征进行了外部验证。最后，我们整合临床特征以建立一个列线图，精确预测生存概率。
维生素B6代谢基因PSAT1可能在淋巴瘤中起保护作用。基于维生素B6代谢特征，我们成功识别出四种不同的DLBCL分子亚型。构建的风险特征有效地评估了患者的风险状态，并结合临床特征建立了列线图。该特征可以精确预测DLBCL患者的1年、3年和5年生存概率，为个体化管理提供重要参考。
本研究基于维生素B6代谢特征识别出了新的DLBCL分子亚型，并建立了具有临床应用价值的风险特征。这些发现为DLBCL患者的精准管理提供了新方向。
