目的 探究血清微小RNA(miR)-155-5p和miR-146b-5p与继发性急性髓系白血病(sAML)染色体畸变及预后的关系。方法 选择2017-05至2020-04空军军医大学第二附属医院血液内科收治的sAML患者26例,另外纳入同期在医院进行体检的健康人25名作为健康对照组。根据国际人类细胞遗传命名系统,将sAML患者分为染色体畸变组和染色体正常组。采用实时荧光定量PCR法检测血清miR-155-5p和miR-146b-5p水平,并记录患者随访期间的总生存期。结果 与健康对照组相比,sAML组患者血清miR-155-5p显著升高[4.69(1.87,30.83)vs. 1.13(0.79,1.78),Z=-4.070,P＜0.001],而miR-146b-5p显著降低[1.79(1.55,2.44)vs. 3.02(2.58,3.43),Z=-4.561,P＜0.001]。二者联合诊断sAML的曲线下面积为0.922(95%CI:0.846～0.997)。与染色体正常组相比,染色体畸变组sAML患者血清miR-155-5p明显升高[19.26(4.45,46.65)vs. 1.51(0.79,3.27),Z=-3.585,P＜0.001],miR-146b-5p明显降低[1.55(1.50,1.97)vs. 2.16(1.79,3.00),Z=-2.954,P=0.003]。血清miR-155-5p和miR-146b-5p水平识别染色体畸变的AUC分别为0.925(95%CI:0.826～1.000)、0.850(95%CI:0.703～0.997),联合AUC可提高至0.919(95%CI:0.812～1.000)。血清miR-155-5p和miR-146b-5p是染色体畸变的独立影响因素(P＜0.05)。血清miR-155-5p高表达(≥4.27)和miR-146b-5p低表达(＜1.62)患者的总生存率更低,中位生存时间更短(P＜0.05)。Cox回归分析结果表明,血清miR-155-5p高表达和miR-146b-5p低表达是sAML患者死亡的独立危险因素(P＜0.05)。结论 血清miR-155-5p高表达和miR-146b-5p低表达与sAML患者染色体畸变和预后不良密切相关,二者有希望成为sAML染色体畸变和预后不良的风险预测指标。
Abstract
Objective To investigate the relationship between serum microRNA(miR-155-5p) and miR-146b-5p and chromosome aberration and prognosis of secondary acute myeloid leukemia (sAML). Methods A total of 26 patients with sAML who were treated in the Department of Hematology of the Second the Second Hospital affiliated to Medical University of PLA Air Force from May 2017 to April 2020 were selected, and 25 healthy people who underwent physical examination in the hospital during the same period were included as healthy control group. According to International System for Human Cytogenetic Nomenclature, sAML patients were divided into chromosome aberrant group and chromosome normal group. The serum levels of miR-155-5p and miR-146b-5p were detected by real-time fluorescence quantitative PCR, and the overall survival of patients during follow-up was recorded. Results Compared with the healthy control group, serum miR-155-5p significantly increased[4.69(1.87,30.83) vs. 1.13(0.79,1.78), Z=-4.070,P＜0.001] and miR-146b-5p significantly decreased [1.79(1.55,2.44) vs. 3.02(2.58,3.43), Z=-4.561, P＜0.001]in the sAML group. The area under the curve of serum miR-155-5p and miR-146b-5p combined diagnosis of sAML was 0.922 (95%CI: 0.846~0.997).Compared with the normal group, the serum miR-155-5p significantly increased [19.26(4.45,46.65) vs. 1.51(0.79,3.27), Z=-3.585,P＜0.001]and miR-146b-5p significantly decreased [1.55(1.50,1.97) vs. 2.16(1.79,3.00), Z=-2.954, P=0.003]in the chromosomal aberration group. The AUC of serum miR-155-5p and miR-146b-5p levels to identify chromosome aberrations was 0.925 (95%CI: 0.826~1.000),0.850(95%CI: 0.703~0.997), and the combined AUC increased to 0.919(95%CI: 0.812~1.000). Multivariate Logistic regression analysis showed that serum miR-155-5p and miR-146b-5p levels were independent influencing factors of chromosome aberration (P＜0.05). Patients with high miR-155-5p expression (≥4.27) and low miR-146b-5p expression (＜1.62) had lower overall survival rate and shorter median survival time (P＜0.05). Cox regression analysis showed that high expression of miR-155-5p and low expression of miR-146b-5p in serum were independent risk factors for death in sAML patients (P＜0.05). Conclusions The high expression of miR-155-5p and the low expression of miR-146b-5p in serum are closely related to chromosome aberration and poor prognosis in sAML patients, and they may be risk predictors of chromosome aberration and poor prognosisof sAML patients.
关键词
微小RNA-155-5p /
微小RNA-146b-5p /
继发性急性髓系白血病 /
染色体畸变 /
预后
Key words
miR-155-5p /
miR-146b-5p /
secondary acute myeloid leukemia /
chromosome aberration /
prognosis
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基金
陕西省自然科学基础研究计划项目(2020JQ-460)
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