Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Clinical Research Center, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hematol Oncol. 2020 Oct;38(4):456-466. doi: 10.1002/hon.2752. Epub 2020 Jun 26.
One-carbon metabolism (OCM) plays a pivotal role in both the stability and integrity of DNA and is mainly regulated by B-vitamins. This study aims to investigate the clinical relevance of B-vitamins and single nucleotide polymorphisms (SNPs) on OCM-related genes in diffuse large B-cell lymphoma (DLBCL). A total of 322 newly diagnosed DLBCL patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone-based immunochemotherapy were recruited into this study. The serum levels of B-vitamins (folate, vitamin B2 [riboflavin], vitamin B6 [pyridoxal 5'-phosphate], and vitamin B12 [cobalamin]), as well as SNPs on methylenetetrahydrofolate reductase, methionine synthase (MTR), MTR reductase (MTRR) and cystathionine gamma-lyase (CTH) genes, were assessed at diagnosis. The prognostic values were estimated using the Kaplan-Meier method and Cox proportional hazards regression methods. Overall, the low serum concentration of folate and vitamin B2, as well as the presence of CTH1364 TT genotype, were significantly associated with poor treatment response in DLBCL. Multivariate analysis indicated that compared with patients in the medium and high serum folate tertiles, low serum folate tertile patients had both significantly inferior progression-free survival (P = .033, Tertile 2 vs Tertile 1, and P = .031, Tertile 3 vs Tertile 1) and overall survival time (P < .001, Tertile 2 vs Tertile 1, and P = .001, Tertile 3 vs Tertile 1). Compared with patients in the medium and high serum vitamin B2 tertiles, low serum vitamin B2 tertile patients had both significantly inferior progression-free survival (P = .006, Tertile 2 vs Tertile 1, and P = .001, Tertile 3 vs Tertile 1) and overall survival time (P = .030, Tertile 2 vs Tertile 1, and P = .255, Tertile 3 vs Tertile 1). In conclusion, alterations in B-vitamin metabolism significantly affected disease progression and had a prognostic impact on DLBCL.
一碳代谢（OCM）在 DNA 的稳定性和完整性中起着关键作用，主要受 B 族维生素调节。本研究旨在探讨 B 族维生素和 OCM 相关基因单核苷酸多态性（SNP）在弥漫性大 B 细胞淋巴瘤（DLBCL）中的临床相关性。本研究共纳入 322 例新诊断的接受利妥昔单抗联合环磷酰胺、多柔比星、长春新碱和泼尼松的基于免疫化疗的 DLBCL 患者。在诊断时评估了 B 族维生素（叶酸、维生素 B2[核黄素]、维生素 B6[吡哆醛 5'-磷酸]和维生素 B12[钴胺素]）的血清水平，以及亚甲基四氢叶酸还原酶、蛋氨酸合酶（MTR）、MTR 还原酶（MTRR）和半胱氨酸γ-裂解酶（CTH）基因上的 SNP。使用 Kaplan-Meier 方法和 Cox 比例风险回归方法估计预后价值。总的来说，叶酸和维生素 B2 血清浓度低，以及 CTH1364 TT 基因型的存在，与 DLBCL 治疗反应不良显著相关。多变量分析表明，与中、高血清叶酸三分位组患者相比，低血清叶酸三分位组患者的无进展生存期（P =.033，三分位 2 与三分位 1，P =.031，三分位 3 与三分位 1）和总生存期（P <.001，三分位 2 与三分位 1，P =.001，三分位 3 与三分位 1）均明显降低。与中、高血清维生素 B2 三分位组患者相比，低血清维生素 B2 三分位组患者的无进展生存期（P =.006，三分位 2 与三分位 1，P =.001，三分位 3 与三分位 1）和总生存期（P =.030，三分位 2 与三分位 1，P =.255，三分位 3 与三分位 1）均明显降低。总之，B 族维生素代谢的改变显著影响疾病的进展，并对 DLBCL 具有预后影响。
