Chen Chao, Dong Quan, Wang Huiqi, Dong Shiqi, Wang Shufan, Lin Wenxin, Jia Chuiming, Dong Mei, Jin Yan, Liu Duo
Department of laboratory, Harbin Medical University Cancer Hospital, 150086, Harbin, China.
Department of Chinese Formulae, Heilongjiang University of Chinese Medicine, 150040, Harbin, China.
Ann Hematol. 2025 Jan;104(1):407-420. doi: 10.1007/s00277-024-06144-6. Epub 2025 Jan 8.
The purpose of this study was to comprehensively analyze the prediction role of NADPH oxidase (NOX)-related polymorphisms (NCF4: rs1883112, CYBA: rs4673, RAC2: rs13058338) and immunohistochemical indices on survival in diffuse large B-cell lymphoma (DLBCL).The impact of NOX polymorphisms were evaluated in 335 DLBCL patients treated with R (rituximab)-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) from Harbin Medical University Cancer Hospital. We also collected information on their immunohistochemical expression and clinical outcomes.Among the patients treated with R-CHOP therapy, the patients with CyclinD1 (+) had significantly shorter progression-free survival (PFS) (p = 0.001) and event-free survival (EFS) (p < 0.001) than CyclinD1 (-) patients. Among patients received CHOP therapy, PFS was significantly longer in CD20 (+) patients (p = 0.011) than in CD20(-) patients. Among the patients treated with R-CHOP therapy, the PFS (p = 0.020) and EFS (p < 0.001) of patients with NCF4 rs1883112 AA/AG genotype were significantly longer than the patients with GG genotype. Patients treated with R-CHOP therapy and with RAC2 rs13058338 AA/AT genotype were more likely to have grade III or higher myelosuppression compared to patients with TT genotype (p = 0.027). Patients treated with CHOP therapy and with RAC2 rs13058338 AA/AT genotype were more likely to have grade III or higher systemic adverse events (p = 0.029). Cox regression analysis showed that NCF4 rs1883112 GG genotype and CyclinD1 (+) were the factors contributing to the poor outcomes in DLBCL patients treated with R-CHOP therapy.In conclusion, the results suggested that the NCF4 rs1883112 G allele may be a poor prognostic biomarker, especially for the DLBCL patients with CD3(-), CD5 (-), CD10 (-), Bcl-2 (+), Bcl-6 (+) or Ki-67(%) < 80%.
本研究旨在全面分析烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶（NOX）相关多态性（NCF4：rs1883112、CYBA：rs4673、RAC2：rs13058338）和免疫组化指标对弥漫性大B细胞淋巴瘤（DLBCL）患者生存的预测作用。对哈尔滨医科大学附属肿瘤医院335例接受R（利妥昔单抗）-CHOP（环磷酰胺、多柔比星、长春新碱和泼尼松）治疗的DLBCL患者评估了NOX多态性的影响。我们还收集了他们的免疫组化表达和临床结局信息。在接受R-CHOP治疗的患者中，细胞周期蛋白D1（CyclinD1）（+）的患者无进展生存期（PFS）（p = 0.001）和无事件生存期（EFS）（p < 0.001）明显短于CyclinD1（-）的患者。在接受CHOP治疗的患者中，CD20（+）患者的PFS（p = 0.011）明显长于CD20（-）的患者。在接受R-CHOP治疗的患者中，NCF4 rs1883112 AA/AG基因型患者的PFS（p = 0.020）和EFS（p < 0.001）明显长于GG基因型患者。与TT基因型患者相比，接受R-CHOP治疗且RAC2 rs13058338 AA/AT基因型的患者更易发生III级或更高等级的骨髓抑制（p = 0.027）。接受CHOP治疗且RAC2 rs13058338 AA/AT基因型的患者更易发生III级或更高等级全身性不良事件（p = 0.029）。Cox回归分析表明，NCF4 rs1883112 GG基因型和CyclinD1（+）是接受R-CHOP治疗的DLBCL患者预后不良的因素。总之，结果表明NCF4 rs1883112 G等位基因可能是一个不良预后生物标志物，尤其对于CD3（-）、CD5（-）、CD10（-）、Bcl-2（+）、Bcl-6（+）或Ki-67（%）< 80%的DLBCL患者。
