循环STAiR18在多发性骨髓瘤患者微小残留监测中的临床应用研究

Study on the clinical application of circulating STAiR18 in the monitoring of minimal residue in patients with multiple myeloma

目的探讨STAiR18作为无创监测新型标志物动态监测多发性骨髓瘤(MM)治疗缓解后体内微小残留病(MRD)的可能性和早诊复发的临床价值。方法收集初诊和治疗后随访患者的骨髓、血浆。采用ELISA测定血浆IL-6水平;提取骨髓浆细胞RNA和循环血浆RNA,通过qRT-PCR分析STAiR18表达水平。化疗后定期随访评估无进展生存率(PFS)和生存期,监测STAiR18表达量。结果共收集46例MM患者,其骨髓浆细胞的STAiR18表达量是对照组的(4.97±1.24)倍(t=2.223,P=0.022),R-ISS分期越差,STAiR18表达量越高(Ⅰ、Ⅱ、Ⅲ期的相对表达量分别为2.49±1.43、5.47±1.14、6.93±1.23)。各期中,STAiR18表达量高于组内均值的患者的PFS均较低于组内均值患者的PFS差(χ^(2)=5.49,P=0.019;χ^(2)=15.96,P<0.05;χ^(2)=0.021,P=0.88)。初诊时,循环STAiR18表达量与骨髓浆细胞STAiR18的表达量显著相关(r=0.99,P<0.0001),也与相同时间点血浆IL-6浓度呈正相关(r=0.88,P<0.0001)。化疗后,11例患者达完全缓解,其中7例患者微小残留监测持续阴性,其STAiR18持续处于较低水平。而另4例患者循环STAiR18表达量逐渐增高,且在多参数流式细胞术MRD报阳前发生显著升高,平均提前4~8周。结论循环STAiR18有望成为MM患者MRD监测的新型无创标志物。

Objective To explore the potential of STAiR18 as a novel non-invasive biomarker for dynamic monitoring of minimal residual disease(MRD)after treatment remission in MM and its clinical value for early diagnosis of relapse.Methods Bone marrow(BM)and plasma samples were collected from patients at the time of initial diagnosis and during follow-up after treatment.Plasma interleukin-6(IL-6)was measured by ELISA.RNA from BM plasma cells and circulating plasma were extracted and STAiR18 expression levels were analyzed through qRT-PCR.Following chemotherapy,regular follow-up assessments were conducted to evaluate progression-free survival(PFS)and overall survival(OS).STAiR18 expression was also monitored.Results Forty-six MM patients were included in the study.The expression level of STAiR18 in their bone marrow plasma cells was(4.97±1.24)times higher compared to the control group(t=2.223,P=0.022).Furthermore,as the R-ISS stage worsened,STAiR18 expression levels increased.The relative expression levels of STAiR18 were(2.49±1.43),(5.47±1.14),and(6.93±1.23)at stage Ⅰ,Ⅱ,and Ⅲ,respectively.In each stage,PFS of patients with STAiR18 expression higher than the mean of the group was lower than that of patients with STAiR18 expression lower than the mean of the group(=5.49,P=0.019 for stage Ⅰ;χ^(2)=15.96,P<0.05 for stage Ⅰ;χ^(2)=0.021,P=0.88 for stage Ⅲ).At the time of initial diagnosis,the circulating STAiR18 expression level showed a significant correlation with the bone marrow plasma cell STAiR18 expression level(r=0.99,P<0.0001)and was also positively correlated with plasma IL-6 concentration at the same time point(r=0.88,P<0.0001).After chemotherapy,11 patients achieved complete remission,with 7 of them maintaining continuous negative MRD status,and their STAiR18 levels remained consistently low.However,in the remaining 4 patients,the circulating STAiR18 expression levels were gradually increased and showed a significant rise before a positive detection in multi-parameter flow cytometry MRD testing.The STAiR18 monitoring was on average 4 to 8 weeks earlier than the MRD testing.Conclusions Circulating STAiR18 is expected to become a novel non-invasive biomarker for monitoring MRD in MM patients.