血浆循环肿瘤DNA与弥漫大B细胞淋巴瘤临床预后的相关性分析  

Correlation between plasma circulating tumor DNA and clinical prognostic characteristics in diffuse large B-cell lymphoma

作　　者：于慧 薄毅文 孙剑声 陈晓丽 孔祥图 倪海雯 YU Hui;BO Yiwen;SUN Jiansheng;CHEN Xiaoli;KONG Xiangtu;NI Haiwen(Department of Hematology,Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing,Jiangsu 210029,China;The First School of Clinical Medicine of Nanjing University of Chinese Medicine,Nanjing,Jiangsu 210029,China)

机构地区：[1]南京中医药大学附属医院血液科,江苏南京210029 [2]南京中医药大学第一临床医学院,江苏南京210029

出　　处：《安徽医药》2025年第3期536-540,I0003,I0004,共7页Anhui Medical and Pharmaceutical Journal

基　　金：国家中医药管理局第四批全国中医优秀人才研修项目(国中医药办人教函〔2017〕24号);江苏省中医药管理局课题项目(YB2017014);江苏省卫生健康委重点项目(ZD2021040)。

摘　　要：目的探讨血浆循环肿瘤DNA(ctDNA)在弥漫大B细胞淋巴瘤(DLBCL)中的表达模式及其与临床预后的相关性,以评估其作为预后生物标志物的潜力。方法回顾性分析2022年6月至2024年1月在南京中医药大学附属医院(江苏省中医院)血液科住院的31例DLBCL病人,利用高通量测序技术(NGS)对血浆ctDNA以及病理组织进行基因突变谱分析。对比分析初诊病人ctDNA突变谱与临床特征、治疗反应及预后之间的关系。对复发难治DLBCL(R/R DLBCL)与初治DLBCL(TN DLBCL)高频突变基因亦进行了初步分析。结果TN DLBCL最常见的突变基因为BTG2(47.8%),BTG1(43.5%),PIM1(39.1%),CARD11(34.8%),B2M(30.4%),BCL6(30.4%)和DUSP2(30.4%)。23例TN DLBCL病人中,16例进行基线ctDNA检测,国际预后指数(IPI)评分高、分期晚、美国东部肿瘤协作组(ECOG)评分高、乳酸脱氢酶(LDH)值高(P=0.020)、β2微球蛋白(B2M)值高(P=0.002)的病人,基线ctDNA水平呈现更高的趋势,16例血浆中多检出154个组织中没有的突变,可以作为组织样本的有效补充,其中有2例组织分型为other的病人,通过基线血浆ctDNA检测可重新分型为MCD亚型。R/R DLBCL总体突变频率不同于TN DLBCL病人。结论ctDNA可作为DLBCL病人临床预后评估的有用生物标志物。未来研究需进一步验证ctDNA在DLBCL预后评估中的临床应用价值。Objective To explore the expression patterns of circulating tumor DNA(ctDNA)in diffuse large B-cell lymphoma(DLBCL)and their correlation with clinical prognostic features,to assess its potential as a prognostic biomarker.Methods A retrospective analysis was conducted on 31 patients with DLBCL hospitalized in the Department of Hematology at the Affiliated Hospital of Nanjing University of Chinese Medicine(Jiangsu Provincial Hospital of Chinese Medicine)from June 2022 to January 2024.High-throughput sequencing technology next generation sequencing(NGS)was used to analyze the gene mutation spectrum of plasma ctDNA and pathological tissues.The relationship between the ctDNA mutation spectrum at initial diagnosis and clinical characteristics,treatment response,and prognosis was compared and analyzed.A preliminary analysis of the high-frequency mutation genes in relapsed/refractory DLBCL(R/R DLBCL)and treatment-naive DLBCL(TN DLBCL)was also performed.Results The most common mutated genes in TN DLBCL were BTG2(47.8%),BTG1(43.5%),PIM1(39.1%),CARD11(34.8%),B2M(30.4%),BCL6(30.4%),and DUSP2(30.4%).Among the 23 TN DLBCL patients,16 underwent baseline ctDNA testing.Patients with high international prognostic index(IPI)scores,advanced staging,high ECOG scores,high LDH values(P=0.020),and high B2M values(P=0.002)tended to have higher baseline ctDNA levels.In 16 plasma samples,154 mutations not found in tissues were detected,which could effectively complement tissue samples.Among them,two cases with tissue typing as‘other’were reclassified as MCD subtype through baseline plasma ctDNA testing.The overall mutation frequency in R/R DLBCL was different from that in TN DLBCL patients.Conclusions ctDNA can serve as a useful biomarker for the clinical prognostic assessment of patients with DLBCL.Further studies are needed to validate the clinical application value of ctDNA in the prognostic assessment of DLBCL.

关 键 词：淋巴瘤 大B细胞 弥漫性 循环肿瘤DNA 基因突变 预后 高通量核苷酸序列分析 

分 类 号：R73[医药卫生—肿瘤]