| 袁冬妹,吴思英,黄素丽,蒋伟超,柯跃斌.血浆miRNA表达与儿童急性淋巴细胞白血病风险的关联研究[J].Chinese journal of Epidemiology,2017,38(9):1252-1258 |
| 血浆miRNA表达与儿童急性淋巴细胞白血病风险的关联研究 |
| Association between expression of plasma miRNA and the risk of childhood acute lymphocytic leukemia |
| Received:December 26, 2016 |
| DOI：10.3760/cma.j.issn.0254-6450.2017.09.022 |
| KeyWord: 儿童急性淋巴细胞白血病 生物标志物 |
| English Key Word: Childhood acute lymphocytic leukemia Biomarker |
| FundProject:国家自然科学基金（81072323） |
| Author Name | Affiliation | E-mail | | Yuan Dongmei | Key Laboratory of Genetics and Molecular Medicine of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China
Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350108, China | | | Wu Siying | Fujian Provincial Key Laboratory of Environment Factors and Cancer, Fujian Medical University, Fuzhou 350108, China | | | Huang Suli | Key Laboratory of Genetics and Molecular Medicine of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China | | | Jiang Weichao | Key Laboratory of Genetics and Molecular Medicine of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China | | | Ke Yuebin | Key Laboratory of Genetics and Molecular Medicine of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China | keyke@szu.edu.cn |
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| Abstract: |
| 目的 探讨miRNA在儿童急性淋巴细胞白血病（cALL）病例血浆中的表达分布特征，分析其与cALL发病风险之间的关系，并判断miRNA作为cALL诊断标记物的可行性。方法 采用病例对照方法，收集2015年1月至2016年11月在深圳市儿童医院确诊初发cALL和骨折病例作为对照各111例，按性别相同和年龄（±1岁）进行1：1匹配，并从中选择4对cALL病例和对照进行LNATM miRNA表达谱芯片检测。采用实时定量PCR验证miRNA表达水平，利用条件logistic回归分析miRNA与cALL发病风险之间的关系，以受试者工作特征曲线（ROC）和重新分类方法分析miRNA作为cALL生物标志物的可行性。结果 芯片筛选出204个差异表达的miRNA。根据入选条件，纳入let-7f-5p、miR-5100、miR-25-3p和miR-3654进行实时定量PCR。病例组let-7f-5p、miR-5100和miR-25-3p的表达水平低于对照组，差异有统计学意义（P<0.01）。在调整混杂因素后，这3个miRNA仍然与cALL的发生存在关联[OR值和95%CI分别为0.84（0.76~0.92）、0.81（0.73~0.90）、0.81（0.74~0.89）]。ROC和重新分类法结果显示与传统危险因素模型相比，加入1个或≥ 2个miRNA均增加曲线下面积（P<0.05），且模型诊断均有增加价值作用（P<0.01）。结论 let-7f-5p、miR-5100、miR-25-3p的表达水平与cALL的发生关联，可作为cALL的生物标志物。 |
| English Abstract: |
| Objective To investigate the characteristics of distribution and expression profiles of plasma miRNA in childhood acute lymphocytic leukemia (cALL) patients; the association between cALL incidence risk and plasma miRNA levels; the feasibility of plasma miRNA serving as cALL diagnostic biomarker. Methods A total of 111 pairs of newly diagnosed cALL patients and patients with fractures were collected from Shenzhen Children's Hospital, China, between January 2015 and November 2016. Age and sex of the cases and controls were 1:1 matched and LNATM miRNA microarray was performed using 4 pairs of cALL and controls selected from the sample population. The expression level of miRNA was validated by real time quantitative PCR. Conditional logistic regression analysis was applied to evaluate the association between miRNA expression levels and the incidence risk of cALL. The receiver operating characteristic curve (ROC) and reclassification analysis were conducted to assess the feasibility of miRNAs serving as biomarkers for cALL. Results A total of 204 differentially expressed miRNA were screened out and let-7f-5p, miR-5100, miR-25-3p and miR-3654 were selected for validation identified according to the inclusion criteria. The expression levels of let-7f-5p, miR-5100 and miR-25-3p in the cALL patients were significantly lower than those of the controls (P<0.01). After adjusting for confounding factors, 3 miRNAs remained significantly associated with the risk of cALL (OR and 95% CI were 0.84 (0.76-0.92), 0.81 (0.73-0.90) and 0.81 (0.74-0.89), respectively. Results from both the ROC analysis and reclassification analysis showed that introduction of one or more miRNA to traditional risk factors improved the area under the curve (P<0.05) and provided additional values to diagnosis (P<0.01). Conclusion The expression levels of let-7f-5p, miR-5100 and miR-25-3p were significantly associated with the incidence rate of cALL, and these miRNAs might serve as promising biomarkers for cALL. |
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