Zhang Ling-Long, An Li, Qi Xiao-Long, Renaguli Abulaiti, Kou Zhen, Tan Wei, Nie Yu-Ling, Muhebaier Abuduer, Li Yan
Department of Hematology, Xinjiang Uygur Autonomous Region People's Hospital, Urumqi 830001, Xinjiang Uygur Autonomous Region, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2024 Dec;32(6):1719-1725. doi: 10.19746/j.cnki.issn.1009-2137.2024.06.013.
To explore the effect of mutation variant allele frequency(VAF) on the prognosis of diffuse large B-cell lymphoma(DLBCL) patients.
This study included 155 patients with DLBCL who were first diagnosed in the People's Hospital of Xinjiang Uygur Autonomous Region from March 2009 to March 2022. Complete clinical data and paraffin-embedded tumor tissue samples were obtained, and DNA was extracted from tumor tissues. The gene mutation profile of DLBCL patients was detected and analyzed by second-generation sequencing technology. Kaplan-Meier method was used to analyze the mutation status of gene and the relationship between mutation VAF and OS. Cox regression univariate and multivariate analysis was use to analyze the independent factors affecting OS. A nornogram model for predicting 1, 3, and 5 years OS in DLBCL patients were established to evaluated the performance of the model based on C-index and calibration curves.
The average value of mutation VAF in male DLBCL patients was significantly higher than that in female patients ( < 0.05). Patients with mutantion had shorter OS than those with wild-type patients ( =0.030). The optimal VAF threshold for mutation based on OS stratification was 33.61% ( < 0.001), and patients with mutation VAF ≥34% had shorter OS than those with mutation VAF < 34% and wild-type patients ( < 0.001). Multivariate Cox analysis showed that mutation VAF≥34% was an independent poor predictor of OS ( =4.05, < 0.001), and IPI score ≥3 was an independent predictor of OS poor ( =2.27, =0.008). In combination with factors with independent prognostic significance obtained from multi-factor analysis, we constructed a nomogram model for predicting 1-year, 3-year, 5-year OS in DLBCL patients. The results showed that the C index of mutation VAF combined with IPI model was 0.743, which predicted the value of 1-year, 3-year, and 5-year OS in DLBCL patients. Calibration curves show that the model has good agreement between predicted and actual survival of DLBCL patients at 1-year, 3-year, and 5-year.
mutation VAF has prognostic value in DLBCL patients, and mutation VAF≥34% is an independent risk factor for OS in DLBCL patients. The prognosis model of mutation VAF combined with IPI nomogram constructed in this study has good predictive performance for DLBCL patients.
探讨突变变异等位基因频率(VAF)对弥漫性大B细胞淋巴瘤(DLBCL)患者预后的影响。
本研究纳入了2009年3月至2022年3月在新疆维吾尔自治区人民医院首次诊断的155例DLBCL患者。获取完整的临床资料和石蜡包埋的肿瘤组织样本,并从肿瘤组织中提取DNA。采用二代测序技术检测并分析DLBCL患者的基因突变谱。采用Kaplan-Meier法分析基因的突变状态以及突变VAF与总生存期(OS)的关系。采用Cox回归单因素和多因素分析来分析影响OS的独立因素。建立预测DLBCL患者1年、3年和5年OS的列线图模型,并基于C指数和校准曲线评估该模型的性能。
男性DLBCL患者的突变VAF平均值显著高于女性患者(P<0.05)。有突变的患者OS短于野生型患者(P=0.030)。基于OS分层的突变最佳VAF阈值为33.61%(P<0.001),突变VAF≥34%的患者OS短于突变VAF<34%的患者和野生型患者(P<0.001)。多因素Cox分析显示,突变VAF≥34%是OS的独立不良预测因素(HR=4.05,P<0.001),国际预后指数(IPI)评分≥3是OS不良的独立预测因素(HR=2.27,P=0.008)。结合多因素分析获得的具有独立预后意义的因素,我们构建了预测DLBCL患者1年、3年、5年OS的列线图模型。结果显示,突变VAF联合IPI模型的C指数为0.743,可预测DLBCL患者1年、3年和5年的OS值。校准曲线显示,该模型在1年、3年和5年时预测的DLBCL患者生存情况与实际生存情况具有良好的一致性。
突变VAF在DLBCL患者中具有预后价值,突变VAF≥34%是DLBCL患者OS的独立危险因素。本研究构建的突变VAF联合IPI列线图预后模型对DLBCL患者具有良好的预测性能。