长链非编码RNA CASC15低表达在伴NPM1基因突变的急性髓系白血病中的临床意义  

Clinical Significance of Low Expression of LncRNA CASC15 in Acute Myeloid Leukemia with NPM1 Mutations

作　　者：夏培慧 徐子浚 金晔 马吉春[1,2] 闻向梅 袁倩[2,3] 冷加燕 钱军 林江 XIA Pei-Hui;XU Zi-Jun;JIN Ye;MA Ji-Chun;WEN Xiang-Mei;YUAN Qian;LENG Jia-Yan;QIAN Jun;LIN Jiang(Laboratory Center,Affiliated People's Hospital of Jiangsu University;Zhenjiang Clinical Research Center of Hematology;Department of Hematology,Affiliated People's Hospital of Jiangsu University,Zhenjiang 212002,Jiangsu Province,China)

机构地区：[1]江苏大学附属人民医院中心实验室 [2]镇江市血液病临床研究中心 [3]江苏大学附属人民医院血液科,江苏镇江212002

出　　处：《中国实验血液学杂志》2022年第3期659-670,共12页Journal of Experimental Hematology

基　　金：国家自然科学基金(81970118,81900163);江苏省医学创新团队(CXTDB2017002);镇江血液学研究中心(SS2018009);镇江社会发展基金会(SH2019065,SH2019067);镇江市第五期169工程科研项目(21)。

摘　　要：目的:确定急性髓系白血病(AML)患者骨髓样本中长链非编码RNA CASC15的表达水平及甲基化水平,并进一步探讨其在AML中的临床意义。方法:纳入82例初治AML患者和18例健康对照者,同时分析了来自GEO和TCGA等7个公共数据集中的CASC15表达和甲基化数据。应用ROC曲线分析确定CASC15表达对AML患者的鉴别意义;使用X-tile方法将患者分为CASC15高表达组和CASC15低表达组,并采用Kaplan-Meier法及单因素和多因素Cox回归分析确定CASC15的预后价值。结果:与健康对照者相比,CASC15在AML患者骨髓细胞中表达显著降低(P<0.001)。ROC曲线分析结果表明,CASC15表达可能是鉴别AML的潜在生物标志物。CASC15在造血过程的早期阶段表达水平较高,在多能祖细胞分化阶段达到峰值,然后迅速下降至低值波动。在FAB亚型中,CASC15在M0中的表达水平显著高于M1-M7。CASC15低表达患者更有可能发生NPM1突变(P=0.048),而高表达患者更易发生IDH1(P=0.021)和RUNX1(P=0.014)突变。在伴NPM1突变的AML患者中,CASC15低表达患者的总体生存时间更短,多因素分析也证实CASC15表达是伴NPM1突变的AML患者总体生存时间的独立影响因素。此外,CASC15在AML患者骨髓样本中的甲基化水平较健康对照者显著降低,高甲基化患者总体生存时间和无病生存时间更短。结论:CASC15在AML中表达降低,并且CASC15低表达提示伴NPM1基因突变的AML预后不良。CASC15在AML中甲基化水平显著降低,高甲基化可能预示患者预后不良。Objective:To identify the expression and methylation patterns of lncRNA CASC15 in bone marrow(BM)samples of acute myeloid leukemia(AML)patients,and further explore its clinical significance.Methods:Eighty-two de novo AML patients and 18 healthy donors were included in the study.Meanwhile,seven public datasets from Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)were included to confirm the expression and methylation data of CASC15.Receiver operating characteristic(ROC)curve analysis was applied to determine the discriminative capacity of CASC15 expression to identify AML.The patients were divided into CASC15;group and CASC15;group by X-tile method,and the prognostic value of CASC15 was identified by Kaplan-Meier method and univariate and multivariate Cox regression analysis.Results:The expression level of CASC15 was significantly decreased in BM cells of AML patients compared with healthy donors(P<0.001).ROC curve analysis suggested that CASC15 expression might be a potential biomarker to discriminate AML from controls.The expression of CASC15 was high at the early stage of hematopoiesis,and reached a peak at the stage of multipotent progenitors differentiation,then decreased rapidly,and was at a range of low level fluctuations in the subsequent process.Among FAB subtypes,CASC15 expression in M0 was significantly higher than that in M1-M7.Clinically,CASC15;patients were more likely to have NPM1 mutations than CASC15;patients(P=0.048),while CASC15;patients had a significantly higher frequency of IDH1 and RUNX1 mutations(P=0.021 and 0.014,respectively).Moreover,CASC15;group had a shorter overall survival(OS)in patients with NPM1 mutations.Furthermore,multivariate analysis confirmed that CASC15 expression was a significant independent risk factor for OS in NPM1 mutated AML patients.In addition,CASC15 methylation level in BM samples of AML patients was significantly decreased compared with healthy donors.Patients with CASC15 high methylation had poor OS and disease-free survival.Conclusion:The expression

关 键 词：CASC15 NPM1 预后 甲基化 急性髓系白血病 

分 类 号：R733.71[医药卫生—肿瘤]