METTL16在多发性骨髓瘤患者中的临床应用价值  

The clinical application value of METTL16 in patients with multiple myeloma

作　　者：汪万杰 许晗 许婷婷 鲍静[1] 夏瑞祥[1] Wang Wanjie;Xu Han;Xu Tingting;Bao Jing;Xia Ruixiang(Dept of Hematology,The First Affiliated Hospital of Anhui Medical University,Hefei 230022)

机构地区：[1]安徽医科大学第一附属医院血液内科,合肥230022

出　　处：《安徽医科大学学报》2024年第4期690-697,共8页Acta Universitatis Medicinalis Anhui

基　　金：安徽省自然科学基金(编号:2008085MH296)。

摘　　要：目的探究甲基转移酶样蛋白16(METTL16)在多发性骨髓瘤(MM)患者临床诊断及对预后预测的应用价值。方法在多发性骨髓瘤研究基金会(MMRF)及基因型-组织表达项目(GTEx)数据库中分析参与N6-甲基腺苷(m6A)修饰的各基因在MM中表达水平及预后潜力。分别收集26例初次诊断MM患者及19例标准方案治疗后MM患者骨髓标本和24例正常人外周血标本,采用qRT-PCR技术测定m6A各基因表达量;同时收集MM初诊患者各实验室及临床指标:血红蛋白(Hb)、白细胞数(WBC)、血小板数(PLT)、血肌酐(Scr)、血清钙离子(Ca^(2+))、β-微球蛋白(β-MG)、骨破坏、ISS分期、分型、生存期(OS),对上述指标进行METTL16相关性分析。进一步检测标本中:白细胞介素(IL)-4、IL-6、IL-10、IL-18及趋化因子(CCL)2、CCL3、CCL4表达水平,并对其与METTL16表达的相关性进行分析。结果数据库分析提示METTL16在MM患者样本中较正常对照表达显著升高,与不良预后相关。qRT-PCR结果显示,MM初诊患者骨髓中METTL16表达水平显著高于治疗后患者以及正常对照组。其表达与血红蛋白、白细胞、骨破坏及分期、生存期等均有相关性,且其表达与CCL4表达呈正相关。结论METTL16在MM患者中高表达,其表达水平与贫血、更严重的骨质破坏及更晚的分期等相关,可能提示不良预后。METTL16与CCL4表达有显著相关性,提示其可能通过相关通路发挥相应致病作用。METTL16在MM的诊疗中将具有重要临床价值。Objective To investigate the value of methyltransferase-like protein 16(METTL16)in the clinical diagnosis and prognostic prediction of multiple myeloma(MM)patients.Methods The expression level and prognostic potential of each gene involved in N6-methyladenosine(m6A)modification in MM were respectively analyzed in the databases of the Multiple Myeloma Research Foundation(MMRF)and the Genotype-Tissue Expression Project(GTEx).Bone marrow specimens from 26 patients with initial diagnosis of MM and 19 patients with MM after treatment with standard regimens and peripheral blood specimens from 24 normal subjects were collected respectively,and the expression levels of m6A genes were determined by qRT-PCR.The correlation between METTL16 expression and various laboratory and clinical indexes was analyzed:hemoglobin(Hb),white blood cell count(WBC),platelet count(PLT),blood creatinine(Scr),serum calcium(Ca^(2+)),β-microglobulin(β-MG),bone destruction,ISS stage,type,and overall survival(OS)in the patients with primary diagnosis.The expression levels of interleukin(IL)-4,IL-6,IL-10,IL-18 and chemokine ligand 2(CCL2),CCL3,CCL4 in the specimens were further examined and their correlation with the expression of METTL16 was investigated.Results Database analysis suggested that METTL16 expression was significantly higher in MM patient samples compared with normal controls,which was associated with poor prognosis and had certain diagnostic value.qRT-PCR results showed that the expression level of METTL16 in the bone marrow of patients with initial diagnosis of MM was significantly higher than that of treated patients and normal controls.Its expression was positively correlated with hemoglobin,leukocytes and stage,and its expression was positively correlated with CCL4 expression.Conclusion METTL16 expression was significantly elevated in patients with MM,and its expression level was correlated with anemia,more bone destruction and worse stage,which might indicate a poor prognosis.The significant correlation between the expression

关 键 词：多发性骨髓瘤 N6-甲基腺苷 甲基转移酶样蛋白16 炎症因子 趋化因子 CCL4 

分 类 号：R733.3[医药卫生—肿瘤]