Prognostic impact of B-vitamins involved in one-carbon metabolism in patients with diffuse large B-cell lymphoma |
| |
| Authors: | Yiwen Cao Peizhan Chen Minci Cai Qing Shi Pengpeng Xu Li Wang Yang He Hui Wang Weili Zhao |
| |
| Affiliation: | 1. 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;2. Clinical Research Center, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, China;3. 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 Pôle de Recherches Sino-Français en Science du Vivant et Génomique, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China;4. School of public health, Shanghai Jiao Tong University School of Medicine, Shanghai, China |
| |
| Abstract: | 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. |
| |
| Keywords: | cystathionine gamma-lyase diffuse large B-cell lymphoma folate prognosis vitamin B2 |
|
|
