主管单位:中华人民共和国
国家卫生健康委员会
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编辑部主任:吴翔宇
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英文作者:Bai Taomin Liu Hong Wang Xia
英文单位:Department of Pediatrics Shaanxi Provincial People′s Hospital Xi′an 710068 China
关键词:急性淋巴细胞白血病;微小RNA-760;细胞质聚腺苷酸化元件结合蛋白2;临床病理特征;预后
英文关键词:Acutelymphoblasticleukemia;MicroRNA-760;Cytoplasmicpolyadenylationelementbindingprotein2;Clinicopathologicalfeatures;Prognosis
目的 探讨急性淋巴细胞白血病(ALL)患儿血清微小RNA-760(miR-760)、细胞质聚腺苷酸化元件结合蛋白2(CPEB2)表达与临床病理特征和预后的关系。方法 前瞻性选取2020年1月至2022年6月陕西省人民医院收治的ALL患儿205例(ALL组),另选取同期健康儿童103例(对照组)。检测血清miR-760、CPEB2 mRNA表达量。通过在线数据库预测miR-760与CPEB2的结合位点。采用Pearson相关分析ALL患儿血清miR-760、CPEB2 mRNA表达的相关性,并分析二者与临床病理特征的关系。比较不同血清miR-760、CPEB2 mRNA表达量患儿无进展生存率。采用多因素Cox回归和受试者工作特征(ROC)曲线分析ALL患儿预后的影响因素及血清miR-760、CPEB2 mRNA表达对其的预测效能。结果 ALL组血清miR-760表达量低于对照组[(0.64±0.11)比(1.01±0.17)],CPEB2 mRNA表达量高于对照组[(1.33±0.30)比(0.83±0.14)](均P<0.001)。miR-760与CPEB2的3′-非翻译端2855-2861处存在结合位点。ALL患儿血清miR-760与CPEB2 mRNA表达呈负相关(r=-0.655,P<0.001)。不同危险分层ALL患儿血清miR-760、CPEB2 mRNA表达量差异均有统计学意义(均P<0.001)。miR-760高表达组ALL患儿3年无病生存率高于miR-760低表达组,CPEB2 mRNA高表达组ALL患儿3年无病生存率低于CPEB2 mRNA低表达组(均P<0.05)。混合谱系白血病基因重排、危险分层高危、CPEB2 mRNA≥1.33均为ALL患儿不良预后的独立危险因素,miR-760≥0.64为独立保护因素(均P<0.05)。血清miR-760、CPEB2 mRNA表达及二者联合预测ALL患儿不良预后的曲线下面积分别为0.796、0.790、0.896,二者联合优于血清miR-760、CPEB2 mRNA表达单独预测效能(均P<0.05)。结论 ALL患儿血清miR-760低表达和CPEB2 mRNA高表达与不良临床病理特征和预后有关,血清miR-760、CPEB2表达联合对预后的预测效能较高。
Objective To investigate the correlation of serum microRNA-760 (miR-760) and cytoplasmic polyadenylation element binding protein 2 (CPEB2) expression with clinicopathological features and prognosis in children with acute lymphoblastic leukemia (ALL). Methods A total of 205 children with ALL admitted to Shaanxi Provincial People′s Hospital from January 2020 to June 2022 were prospectively enrolled as the ALL group, and 103 healthy children during the same period were selected as the control group. The serum expression levels of miR-760 and CPEB2 mRNA were detected. The binding site between miR-760 and CPEB2 was predicted through an online database. Pearson correlation analysis was used to analyze the correlation between serum miR-760 and CPEB2 mRNA expression in children with ALL, and their relationship with clinicopathological features was also analyzed. The progression-free survival rate was compared among children with different serum expression levels of miR-760 and CPEB2 mRNA. Multivariate Cox regression analysis and receiver operating characteristic (ROC) curve were used to analyze the influencing factors for the prognosis of children with ALL and the predictive efficacy of serum miR-760 and CPEB2 mRNA expression for prognosis. Results The serum expression level of miR-760 in the ALL group was lower than that in the control group [(0.64±0.11) vs (1.01±0.17)], and the expression level of CPEB2 mRNA was higher than that in the control group [(1.33±0.30) vs (0.83±0.14)](all P<0.001). A binding site of miR-760 was found at positions 2855-2861 of the 3′untranslated region of CPEB2. Serum miR-760 expression was negatively correlated with CPEB2 mRNA expression in children with ALL (r=-0.655, P<0.001). There were statistically significant differences in the serum expression levels of miR-760 and CPEB2 mRNA among ALL children with different risk stratifications (all P<0.001). The 3-year event-free survival rate of ALL children in the miR-760 high expression group was higher than that in the miR-760 low expression group, and the 3-year event-free survival rate in the CPEB2 mRNA high expression group was lower than that in the CPEB2 mRNA low expression group (all P<0.05). Mixed lineage leukemia gene rearrangement, high-risk stratification and CPEB2 mRNA ≥1.33 were independent risk factors for poor prognosis in children with ALL, while miR-760 ≥0.64 was an independent protective factor (all P<0.05). The areas under the curve of serum miR-760, CPEB2 mRNA and their combination in predicting poor prognosis of children with ALL were 0.796, 0.790 and 0.896, respectively. The combined detection was superior to the single detection of serum miR-760 or CPEB2 mRNA in predictive efficacy (all P<0.05). Conclusion Serum miR-760 low expression and CPEB2 mRNA high expression are associated with adverse clinicopathological features and poor prognosis in children with ALL, and the combined detection of serum miR-760 and CPEB2 expression has a high predictive efficacy for the prognosis of these children.
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