Abstract：
Neuroblastoma (NB) accounts for 15% of all pediatric cancer fatalities (NB). Biomarkers that facilitate early NB detection are needed because by the time of diagnosis, over half of NBs had spread. MicroRNA-21(miR-21) and miR-155 are involved in cancer biology due to their immune modulation functions. Altered monocyte subset distribution is thought to be involved in a number of solid tumors due to its immunological role. We aimed to investigate the expression levels of miR-21 and miR-155 and their association with circulating monocytes subsets in NB and to evaluate if they correlate to the disease pathogenesis and outcome.
METHODS: This case control study involved 79 children classified into 39 newly diagnosed NB children and 40 age and sex matched healthy children. Real-time PCR was used to assess the expression of plasma miR-21 and miR-155. The frequency of circulating monocytes subsets was assessed by flow cytometry.
RESULTS: NB group showed significant up-regulation in expression of miR-21(20.9 folds) and miR-155 (1.8 folds) when compared to the control group (p < 0.001) and (p = 0.02) respectively. Also, frequency of circulating intermediate monocytes revealed significant up regulation in children with NB. In NB patients, there was a positive correlation between miR-21 and frequency of total and intermediate monocytes (r = 0.5 p < 0.001 and r = 0.7, p < 0.001, respectively). We found no discernible differences when we compared study markers between the high risk and intermediate risk groups. In addition, no significant difference was seen in study markers when patients were sub-grouped according to their induction treatment response. ROC curve analysis revealed that miR-21 up-regulation distinguished NB in childhood at an AUC of 0.94 (82% sensitivity and 100% specificity) while miR-155 up-regulation had less capacity to distinguish NB in childhood at an AUC of 0.65 (38% sensitivity and 93% specificity).
CONCLUSIONS: miR-21 can be utilized as a sensitive biomarker for childhood NB development. In pediatric NB, miR-21 was linked to intermediate monocyte plasticity. Both, miR-21 and miR-155 had no impact on NB outcome.
METHODS: This case control study involved 79 children classified into 39 newly diagnosed NB children and 40 age and sex matched healthy children. Real-time PCR was used to assess the expression of plasma miR-21 and miR-155. The frequency of circulating monocytes subsets was assessed by flow cytometry.
RESULTS: NB group showed significant up-regulation in expression of miR-21(20.9 folds) and miR-155 (1.8 folds) when compared to the control group (p < 0.001) and (p = 0.02) respectively. Also, frequency of circulating intermediate monocytes revealed significant up regulation in children with NB. In NB patients, there was a positive correlation between miR-21 and frequency of total and intermediate monocytes (r = 0.5 p < 0.001 and r = 0.7, p < 0.001, respectively). We found no discernible differences when we compared study markers between the high risk and intermediate risk groups. In addition, no significant difference was seen in study markers when patients were sub-grouped according to their induction treatment response. ROC curve analysis revealed that miR-21 up-regulation distinguished NB in childhood at an AUC of 0.94 (82% sensitivity and 100% specificity) while miR-155 up-regulation had less capacity to distinguish NB in childhood at an AUC of 0.65 (38% sensitivity and 93% specificity).
CONCLUSIONS: miR-21 can be utilized as a sensitive biomarker for childhood NB development. In pediatric NB, miR-21 was linked to intermediate monocyte plasticity. Both, miR-21 and miR-155 had no impact on NB outcome.
摘要：
神经母细胞瘤（NB）占所有儿科癌症死亡人数（NB）的15％。需要有助于早期NB检测的生物标志物，因为到诊断时，超过一半的NB已经扩散。MicroRNA-21(miR-21)和miR-155由于其免疫调节功能而参与癌症生物学。由于其免疫学作用，改变的单核细胞亚群分布被认为与许多实体瘤有关。我们旨在研究miR-21和miR-155的表达水平及其与NB中循环单核细胞亚群的关联，并评估它们是否与疾病的发病机制和结果相关。
方法：本病例对照研究纳入79名儿童，分为39名新诊断的NB儿童和40名年龄和性别匹配的健康儿童。使用实时PCR评估血浆miR-21和miR-155的表达。通过流式细胞术评估循环单核细胞亚群的频率。
结果:NB组分别与对照组(p<0.001)和(p=0.02)相比,显示miR-21(20.9倍)和miR-155(1.8倍)的表达显著上调。此外，循环中间单核细胞的频率显示在患有NB的儿童中显著上调。在NB患者中，miR-21与总单核细胞和中间单核细胞的频率呈正相关(分别为r=0.5p<0.001和r=0.7,p<0.001)。当我们比较高风险和中等风险组之间的研究标记时，我们没有发现明显的差异。此外,当根据诱导治疗反应对患者进行亚组时,在研究标志物中没有观察到显著差异.ROC曲线分析揭示miR-21上调在0.94的AUC(82%灵敏度和100%特异性)区分儿童中的NB,而miR-155上调在0.65的AUC(38%灵敏度和93%特异性)区分儿童中的NB的能力较低。
结论：miR-21可用作儿童NB发育的敏感生物标志物。在儿科NB中，miR-21与中等单核细胞可塑性相关。两者,miR-21和miR-155对NB结果无影响。
方法：本病例对照研究纳入79名儿童，分为39名新诊断的NB儿童和40名年龄和性别匹配的健康儿童。使用实时PCR评估血浆miR-21和miR-155的表达。通过流式细胞术评估循环单核细胞亚群的频率。
结果:NB组分别与对照组(p<0.001)和(p=0.02)相比,显示miR-21(20.9倍)和miR-155(1.8倍)的表达显著上调。此外，循环中间单核细胞的频率显示在患有NB的儿童中显著上调。在NB患者中，miR-21与总单核细胞和中间单核细胞的频率呈正相关(分别为r=0.5p<0.001和r=0.7,p<0.001)。当我们比较高风险和中等风险组之间的研究标记时，我们没有发现明显的差异。此外,当根据诱导治疗反应对患者进行亚组时,在研究标志物中没有观察到显著差异.ROC曲线分析揭示miR-21上调在0.94的AUC(82%灵敏度和100%特异性)区分儿童中的NB,而miR-155上调在0.65的AUC(38%灵敏度和93%特异性)区分儿童中的NB的能力较低。
结论：miR-21可用作儿童NB发育的敏感生物标志物。在儿科NB中，miR-21与中等单核细胞可塑性相关。两者,miR-21和miR-155对NB结果无影响。
