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非霍奇金淋巴瘤患者MS4A1基因多态性与利妥昔单抗血药浓度及疗效的相关性研究
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| 篇名： | 非霍奇金淋巴瘤患者MS4A1基因多态性与利妥昔单抗血药浓度及疗效的相关性研究 |
| TITLE： | Study on relationships of MS4A1 gene polymorphism with blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma |
| 摘要： | 目的 探索非霍奇金淋巴瘤患者MS4A1基因多态性对利妥昔单抗血药浓度及疗效的影响。方法选择2016年1月至2020年12月在中山大学肿瘤防治中心接受R-CHOP方案的新确诊非霍奇金淋巴瘤患者160例进行前瞻性观察性研究，最短随访时间约5年。以酶联免疫吸附试验测定患者利妥昔单抗血药浓度。采用Haploview4.2软件挑选MS4A1基因位点：rs1051461、rs17155034、rs4939364、rs10501385，以基质辅助激光解吸电离-飞行时间质谱法分析患者的基因型。采用单因素线性回归分析患者各因素（人口统计学、临床指标与基因型）与第1个疗程利妥昔单抗稳态谷浓度的相关性，并进行多元线性回归分析。绘制Kaplan-Meier曲线以评估患者的无进展生存期（PFS）和总生存期（OS）。以MS4A1基因型和肿瘤分期为自变量，采用Cox回归模型评估影响患者预后的因素。结果携带MS4A1rs10501385CC基因型患者的利妥昔单抗血药浓度为15.20μg/mL，显著低于AA+AC型患者的21.95μg/mL（P＜0.05）。以患者肿瘤分期和MS4A1rs10501385基因多态性建立的利妥昔单抗血药浓度多元线性回归模型能解释7.3%的个体差异。与携带MS4A1rs1051461CC基因型患者比较，CT+TT基因型患者的PFS和OS均显著延长（P＜0.05）。Cox回归模型显示，MS4A1rs1051461CC基因型（HR＝4.406，95%CI为1.743～11.137，P＜0.05）和肿瘤分期Ⅲ或Ⅳ期（HR＝3.233，95%CI为1.413～7.399，P＜0.05）是影响患者PFS的独立危险因素。结论非霍奇金淋巴瘤患者的肿瘤分期和MS4A1rs10501385位点多态性是利妥昔单抗血药浓度的关键影响因素，而肿瘤分期和MS4A1rs1051461位点多态性能显著影响非霍奇金淋巴瘤患者的PFS。 |
| ABSTRACT： | OBJECTIVE To explore the effects of CD20 coding gene （MS4A1） polymorphism on the blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma. METHODS A prospective observational study was conducted on 160 newly diagnosed non-Hodgkin’s lymphoma patients who received the R-CHOP regimen at the Sun Yat Sen University Cancer Center from January 2016 to December 2020， with a minimum follow-up period of approximately 5 years. The blood concentration of rituximab was detected by enzyme-linked immunosorbent assay. MS4A1 tagSNPs were selected by Haploview4.2 software， including rs1051461， rs17155034， rs4939364， and rs10501385. The genotype of MS4A1 was detected by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Univariate linear regression analysis was employed to examine the correlation between various factors（demographic， clinical， and genotypic variables） in patients and the steady-state trough concentration of rituximab during the first course of treatment， followed by multivariate linear regression analysis. Kaplan-Meier curves were drawn to evaluate progression-free survival （PFS） and overall survival （OS）. Using MS4A1 genotype and tumor stage as independent variables， Cox regression model was employed to evaluate the factors influencing patient prognosis. RESULTS The blood concentration of rituximab in MS4A1 rs10501385 CC carriers was 15.20 μg/mL，which was significantly lower than 21.95 μg/mL in AA+AC carriers （P＜0.05）. The multivariate linear regression model incorporating tumor stage and MS4A1 rs10501385 polymorphism explained 7.3% of the interindividual variability in rituximab concentrations. Compared with MS4A1 rs1051461 CC carriers， CT+TT carriers had significantly prolonged PFS and OS （P＜0.05）. The Cox proportional hazards regression model showed that the MS4A1 rs1051461 CC genotype （HR＝4.406， 95%CI：1.743-11.137， P＜0.05） and tumor Ⅲ&Ⅳ （HR＝3.233， 95%CI： 1.413-7.399， P＜0.05） were independent risk factors for PFS. CONCLUSIONS The tumor staging and MS4A1 rs10501385 polymorphism are key influencing factors for blood concentration of rituximab， and MS4A1 rs1051461 polymorphism significantly affects PFS in non-Hodgkin’s lymphoma patients. |
| 期刊： | 2025年第36卷第13期 |
| 作者： | 石凤；刘韬；黄河；房财富；管少兴；张璋；王钊；方小洁；陈卓佳；刘澍 |
| AUTHORS： | SHI Feng，LIU Tao，HUANG He， FANG Caifu，GUAN Shaoxing，ZHANG Zhang，WANG Zhao，FANG Xiaojie，CHEN Zhuojia，LIU Shu |
| 关键字： | 利妥昔单抗；非霍奇金淋巴瘤；MS4A1基因；基因多态性；血药浓度；疗效 |
| KEYWORDS： | rituximab； non-Hodgkin’s lymphoma； MS4A1； genetic polymorphism； blood concentration； efficacy |
| 阅读数： | 3 次 |
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