CD24抗原在多发性骨髓瘤患者中的表达和诱导治疗疗效的预测价值

The expression of CD24 antigen in multiple myeloma patients and its predictive value after induction therapy

目的分析CD24抗原在多发性骨髓瘤(MM)患者骨髓浆细胞(BMPC)上表达情况以及诱导治疗疗效的预测价值。方法观察性研究。本研究标本均来自2022年8月12日至2024年2月1日期间就诊于首都医科大学附属北京积水潭医院血液科258例MM患者。按疾病不同阶段分为新诊断MM(NDMM)共78例[男42例、女36例、年龄(62±11)岁]、复发难治组56例(男34例、女22例、年龄64±9岁)、疾病缓解组124例[男68例、女56例、年龄(62±10)岁]。以多参数流式细胞术(MFC)检测MM患者BMPC上CD24抗原表达水平作为研究对象,分析CD24表达与MM疾病状态的关系。回顾性分析78例NDMM患者初诊时临床资料及实验室结果,包括性别、年龄、MFC检测目的抗原CD24及对照抗原(包括CD19、CD20、CD24、CD27、CD56)的结果、诱导治疗后评效、ISS分期、R-ISS分期、血红蛋白、β2微球蛋白、人血白蛋白,血肌酐、乳酸脱氢酶、校正血钙、BMPC比例、FISH检测结果。以NDMM患者初诊时MFC检测BMPC上CD24及对照抗原阳性率作为研究对象,按照诱导治疗评效不同分为深度缓解组[包括完全缓解(CR)和非常好的部分缓解(VGPR)]共43例,非深度缓解组(非CR和VGPR)共17例,采用单因素分析对比两组患者BMPC上各抗原表达的差异,二元Logistic回归分析患者初诊时抗原表达与诱导治疗后疗效的关系。以NDMM患者初诊时CD24阳性率和诱导治疗后是否达深度缓解作为研究对象,利用受试者工作特征(ROC)曲线分析CD24对NDMM患者诱导治疗后达深度缓解的预测价值,同时得出最佳临界值。依据临界值将NDMM分成两组,比较两组间临床基线资料和预后指标之间的差异。结果NDMM、复发难治组、疾病缓解组的浆细胞CD24阳性率分别是2.18%(95%CI 0.08%~81.85%)、3.81%(95%CI 0.10%~64.56%)、8.74%(95%CI 0.79%~95.55%)。与疾病缓解组相比,NDMM和复发难治组的浆细胞CD24阳性率更低(Z分别为-7.889,-5.282,P均<0.001)。单因素分析结果显示深度缓解组与非深度缓解组之间初诊CD24阳性率差异具有统计学意义(Z=-3.265,P<0.001),而两组CD19(Z=-0.271,P=0.787)、CD20(Z=-0.205,P=0.837)、CD27(Z=-0.582,P=0.560)、CD56(Z=-0.328,P=0.743)差异均无统计学意义。二元Logistic回归结果显示与对照抗原[CD19(OR=1.04595%CI 0.975~1.120,P=0.217)、CD20(OR=1.000,95%CI 0.971~1.030,P=0.976)、CD27(OR=0.997,95%CI 0.977~1.016,P=0.734)、CD56(OR=1.006,95%CI 0.990~1.006,P=0.449)]相比,NDMM患者浆细胞CD24的表达(OR=0.423,95%CI 0.215~0.423,P=0.013)与诱导治疗后是否达深度缓解的关系最为密切,初诊时CD24比例越低诱导治疗后达深度缓解的概率越小。CD24预测诱导治疗后评效达深度缓解的曲线下面积(AUC)为0.772(95%CI 0.655~0.889,P=0.001),敏感度60.50%,特异度85.00%,最佳临界值为2.21%。与浆细胞CD24阳性率≥2.21%组相比,浆细胞CD24阳性率<2.21%组的男性占比较高(39.47%对65.00%,χ^(2)=5.092,P=0.024)、ISS分期Ⅲ期占比更高(41.67%对58.33%,χ^(2)=6.175,P=0.046)、β2微球蛋白较高(3.19 mg/L对4.14 mg/L,Z=-2.257,P=0.024)、MFC检测BMPC占比也较高[(8.672±1.827)%对(19.530±3.188)%,t=-2.963,P=0.004]。结论浆细胞CD24阳性率低与MM患者较高的肿瘤负荷及较差的疾病状态密切相关。初诊时CD24阳性率可以预测诱导治疗后疗效,CD24比例低诱导治疗后疗效差。

ObjectiveThis study analyzed the expression of CD24 antigen on bone marrow plasma cells(BMPC)of patients with multiple myeloma(MM)and the predictive value of induction therapy.MethodsThis clinical observational study utilized 258 MM patients samples treated at the Hematology Department of Beijing Jishuitan Hospital who met the inclusion criteria in the Department of Hematology,Capital Medical University,from August 12th,2022 to February 1st,2024.According to the different stages of the disease,patients were divided into three groups:78 cases of Newly Diagnosed Multiple Myeloma(NDMM)(42 males and 36 females,aged 62±11),56 cases of the relapse refractory group(34 males and 22 females,aged 64±9),and 124 cases of the disease remission group(68 males and 56 females,aged 62±10).Multiparameter flow cytometry(MFC)was used to detect the expression level of CD24 antigen on BMPC and the relationship between CD24 and MM disease status.The clinical data and test results of 78 NDMM patients at initial diagnosis were retrospectively analyzed,including gender,age,MFC detection of the positive expression rate of antigens(CD19,CD20,CD24,CD27,CD56),the results of efficacy evaluation after induction therapy,ISS staging,R-ISS staging,blood hemoglobin,β2-microglobulin,human serum albumin,serum creatinine,lactate dehydrogenas,correction of calcium,BMPC ratio,and the results of FISH.The patients were divided into a deep remission group[including complete remission(CR)and very good partial remission(VGPR)]with 43 cases and a non-deep remission group(non CR and VGPR)with 17 cases according to the difference of antigen positive expression rate after induction therapy.The differences of antigen expression on BMPC between the two groups were compared.Binary logistic regression was used to analyze the relationship between the expression of each antigen and the efficacy after induction therapy in patients,and the results showed that CD24 was more correlated with the achievement of deep remission after induction therapy than other antigens.Therefore,taking the positive expression rate of CD24 in NDMM patients at the initial diagnosis and deep remission after induction therapy as the research objects,the predictive value of CD24 for NDMM patients reaching deep remission after induction therapy was analyzed by using receiver operating characteristic curve(ROC),and the optimal cutoff value was obtained.NDMM was divided into two groups according to the cut-off value,and the differences between the two groups in clinical baseline data and prognostic indicators were compared.ResultsThe positive rates of plasma cell CD24 expression in the NDMM group,the relapse refractory group and the disease remission group were 2.18(95%CI 0.08-81.85)%,3.81(95%CI 0.10-64.56)%,8.74(95%CI 0.79-95.55)%respectively.Compared with the disease remission group,the NDMM and relapse refractory group was lower(Z=-7.889,-5.282,respectively,P<0.001).Univariate analysis showed that there was a significant difference in the positive expression rate of CD24 at initial diagnosis between the deep remission group and the non-deep remission group(Z=-3.265,P<0.001),while there was no significant difference in CD19(Z=-0.271,P=0.787),CD20(Z=-0.205,P=0.837),CD27(Z=-0.582,P=0.560),and CD56(Z=-0.328,P=0.743)between the two groups.Binary logistic regression analysis showed that compared with other antigens[CD19(OR=1.045,95%CI 0.975-1.120,P=0.217),CD20(OR=1.000,95%CI 0.971-1.030,P=0.976),CD27(OR=0.997,95%CI 0.977-1.016,P=0.734),CD56(OR=1.006,95%CI 0.990-1.006,P=0.449)],the expression of CD24(OR=0.423,95%CI 0.990-1.006,P=0.449)on BMPC in NDMM patients was most closely related to the achievement of deep remission was achieved after induction therapy.The lower the proportion of CD24 at the initial diagnosis was,the lower the probability of achieving deep remission after induction therapy was.The area under the curve(AUC)of CD24 in predicting deep remission after induction therapy was 0.772(95%CI 0.655-0.889,P=0.001),with a sensitivity of 60.50%,a specificity of 85.00%,and the optimal critical value was 2.21%.Compared with the group with plasma CD24 positive rate>2.21%,the group with plasma CD24 positive rate<2.21%had a higher proportion of male(39.47%vs 65.00%,χ^(2)=5.092,P=0.024),ISS stagingⅢ(41.67%vs 58.33%,χ^(2)=6.175,P=0.046),β2 microglobulin(3.19 mg/L vs 4.14 mg/L,Z=-2.257,P=0.024),and BMPC[(8.672±1.827)%vs(19.530±3.188)%,t=-2.963,P=0.004]detected by MFC,and the differences were statistically significant.ConclusionsThe low positive rate of plasma cell CD24 is closely related to the higher tumor burden and the worse disease status of MM patients.In addition,the positive expression rate of CD24 is at initial diagnosis can predict the efficacy achieved after induction therapy,and the lower positive rate of CD24 is,the worse the efficacy achieved after induction therapy.At the same time,MFC detection of CD24 is convenient and efficient in the evaluation and prediction of MM.