目的 探讨血清miR-922及miR-506表达水平对儿童急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)诊断及预后判断的价值。 方法 前瞻性选取132例ALL患儿(ALL组)和80例健康儿童(健康对照组)纳入本研究,采用实时荧光定量PCR技术检测ALL组和健康对照组血清miR-922及miR-506表达水平。绘制受试者工作特征曲线分析miR-922及miR-506对儿童ALL的诊断价值。应用Kaplan-Meier法绘制生存曲线,采用多因素COX回归模型分析影响ALL患儿预后不良的因素。 结果 ALL组血清miR-922及miR-506表达水平均明显高于健康对照组(P<0.001)。受试者工作特征曲线分析结果显示,miR-922及miR-506诊断儿童ALL的最佳截断值分别为1.46、2.17。miR-922高表达组(≥1.46)及miR-506高表达组(≥2.17)的淋巴结肿大、白细胞计数≥50×109/L、中高危险度分层、MLL基因重排、染色体核型异常的发生率均明显高于miR-922及miR-506低表达组(P<0.05)。Kaplan-Meier分析结果显示,miR-922及miR-506高表达与ALL患儿生存期短有关(P<0.05)。多因素COX回归分析结果显示,白细胞计数≥50×109/L、危险度分层为中高危、MLL基因重排、miR-922≥1.46及miR-506≥2.17可提示ALL患儿预后不良(P<0.05)。 结论 miR-922及miR-506表达水平对儿童ALL诊断及预后判断均有较好的价值。
Abstract
Objective To study the value of serum miR-922 and miR-506 expression levels in the diagnosis and prognostic assessment of childhood acute lymphoblastic leukemia (ALL). Methods A total of 132 children with ALL (ALL group) and 80 healthy children (healthy control group) were prospectively selected in this study. Quantitative real-time polymerase chain reaction was used to measure the expression levels of serum miR-922 and miR-506 in both groups. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic value of miR-922 and miR-506 for childhood ALL. The Kaplan-Meier method was used to plot survival curves, and multivariate COX regression models were used to analyze the risk factors for poor prognosis in children with ALL. Results The ALL group had significantly higher expression levels of serum miR-922 and miR-506 than the control group (P<0.001). The ROC curve analysis showed that the optimal cut-off values of miR-922 and miR-506 for the diagnosis of childhood ALL were 1.46 and 2.17, respectively. The high miR-922 expression (≥1.46) group and high miR-506 expression (≥2.17) group had significantly higher incidence rates of lymph node enlargement, leukocyte count ≥50×109/L, medium-high risk stratification, mixed-lineage leukemia (MLL) gene rearrangement, and karyotype abnormality than the low miR-922 expression group and low miR-506 expression group (P<0.05). The Kaplan-Meier analysis showed that high expression of miR-922 and miR-506 was associated with short survival time in children with ALL (P<0.05). The multivariate COX regression analysis showed that leukocyte count ≥50×109/L, medium-high risk stratification, MLL gene rearrangement, miR-922≥1.46, and miR-506≥2.17 could indicate poor prognosis in children with ALL (P<0.05). Conclusions The expression levels of miR-922 and miR-506 are of good value in the diagnosis and prognostic assessment of childhood ALL.
关键词
急性淋巴细胞白血病 /
miR-922 /
miR-506 /
诊断价值 /
预后 /
儿童
Key words
Acute lymphoblastic leukemia /
miR-922 /
miR-506 /
Diagnostic value /
Prognosis /
Child
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参考文献
1 Brown P, Inaba H, Annesley C, et al. Pediatric acute lymphoblastic leukemia, version 2.2020, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2020, 18(1): 81-112. PMID: 31910389. DOI: 10.6004/jnccn.2020.0001.
2 Shafik RE, Abd El Wahab N, Mokhtar MM, et al. Expression of microRNA-181a and microRNA-196b in Egyptian pediatric acute lymphoblastic leukemia[J]. Asian Pac J Cancer Prev, 2020, 21(11): 3429-3434. PMID:33247705. PMCID:PMC8033117. DOI: 10.31557/APJCP.2020.21.11.3429.
3 Moussa Agha D, Rouas R, Najar M, et al. Identification of acute myeloid leukemia bone marrow circulating microRNAs[J]. Int J Mol Sci, 2020, 21(19): 7065. PMID:32992819. PMCID:PMC7583041. DOI: 10.3390/ijms21197065.
4 Amankwah EK, Devidas M, Teachey DT, et al. Six candidate miRNAs associated with early relapse in pediatric B-cell acute lymphoblastic leukemia[J]. Anticancer Res, 2020, 40(6): 3147-3153. PMID: 32487609. PMCID: PMC7722248. DOI: 10.21873/anticanres.14296.
5 Zhu XW, Wang J, Zhu MX, et al. MicroRNA-506 inhibits the proliferation and invasion of mantle cell lymphoma cells by targeting B7H3[J]. Biochem Biophys Res Commun, 2019, 508(4): 1067-1073. PMID: 30553455. DOI: 10.1016/j.bbrc.2018.12.055.
6 中华医学会儿科学分会血液学组, 《中华儿科杂志》编辑委员会. 儿童急性淋巴细胞白血病诊疗建议(第四次修订)[J]. 中华儿科杂志, 2014, 52(9): 641-644. DOI: 10.3760/cma.j.issn.0578-1310.2014.09.001.
7 鲍亮, 吴南海, 吴敏媛, 等. CCLG-ALL2008方案治疗儿童急性淋巴性白血病单中心疗效分析[J]. 中国小儿血液与肿瘤杂志, 2016, 21(2): 66-72. DOI: 10.3969/j.issn.1673-5323.2016.02.003.
8 Capria S, Molica M, Mohamed S, et al. A review of current induction strategies and emerging prognostic factors in the management of children and adolescents with acute lymphoblastic leukemia[J]. Expert Rev Hematol, 2020, 13(7): 755-769. PMID: 32419532. DOI: 10.1080/17474086.2020.1770591.
9 Mardani R, Jafari Najaf Abadi MH, Motieian M, et al. MicroRNA in leukemia: tumor suppressors and oncogenes with prognostic potential[J]. J Cell Physiol, 2019, 234(6): 8465-8486. PMID: 30515779. DOI: 10.1002/jcp.27776.
10 Nair RA, Verma VK, Beevi SS, et al. MicroRNA signatures in blood or bone marrow distinguish subtypes of pediatric acute lymphoblastic leukemia[J]. Transl Oncol, 2020, 13(9): 100800. PMID: 32531485. PMCID: PMC7292917. DOI: 10.1016/j.tranon.2020.100800.
11 Sharifi H, Jafari Najaf Abadi MH, Razi E, et al. MicroRNAs and response to therapy in leukemia[J]. J Cell Biochem, 2019, 120(9): 14233-14246. PMID: 31081139. DOI: 10.1002/jcb.28892.
12 Rostami Yasuj S, Obeidi N, Khamisipou G, et al. Overexpression of miR-506 in Jurkat (acute T cell leukemia) cell line[J]. Iran J Pathol, 2020, 15(4): 282-291. PMID: 32944040. PMCID: PMC7477680. DOI: 10.30699/ijp.2020.119627.2298.
13 Ultimo S, Martelli AM, Zauli G, et al. Roles and clinical implications of microRNAs in acute lymphoblastic leukemia[J]. J Cell Physiol, 2018, 233(8): 5642-5654. PMID: 29154447. DOI: 10.1002/jcp.26290.
14 Rashed WM, Hamza MM, Matboli M, et al. MicroRNA as a prognostic biomarker for survival in childhood acute lymphoblastic leukemia: a systematic review[J]. Cancer Metastasis Rev, 2019, 38(4): 771-782. PMID: 31807971. DOI: 10.1007/s10555-019-09826-0.
15 Tapeh BEG, Alivand MR, Solali S. The role of microRNAs in acute lymphoblastic leukaemia: from biology to applications[J]. Cell Biochem Funct, 2020, 38(4): 334-346. PMID: 31833074. DOI: 10.1002/cbf.3466.
16 王瑞仓, 杨洁, 张晓霞, 等. Hsa-miR-9在儿童急性淋巴细胞白血病中的表达及与CDX2基因的相关性研究[J]. 中国实验血液学杂志, 2020, 28(5): 1523-1527. DOI: 10.19746/j.cnki.issn1009-2137.2020.05.016.
17 金芬芬, 梅妍妍, 王凯玲, 等. 联合检测E2F3a和CASP8AP2表达水平在儿童急性淋巴细胞白血病预后中的意义[J]. 中华实用儿科临床杂志, 2018, 33(9): 697-701. DOI: 10.3760/cma.j.issn.2095-428X.2018.09.011.
18 Ranjbar R, Karimian A, Aghaie Fard A, et al. The importance of miRNAs and epigenetics in acute lymphoblastic leukemia prognosis[J]. J Cell Physiol, 2019, 234(4): 3216-3230. PMID: 29384211. DOI: 10.1002/jcp.26510.