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循环血清肿瘤 miRNA 在小儿毛细胞型星形细胞瘤患者中预测壁结节体积。

Circulating serum oncologic miRNA in pediatric juvenile pilocytic astrocytoma patients predicts mural nodule volume.

机构信息

Division of Neurosurgery, Connecticut Children's Medical Center, 282 Washington St, Hartford, CT, 06106, USA.

Department of Surgery, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT, 06032, USA.

出版信息

Acta Neurochir (Wien). 2018 Aug;160(8):1571-1581. doi: 10.1007/s00701-018-3589-6. Epub 2018 Jun 18.

DOI:10.1007/s00701-018-3589-6
PMID:29911246
Abstract

BACKGROUND

Juvenile pilocytic astrocytomas represent the largest group of pediatric brain tumors. The ideal management for these tumors is early, total surgical resection. To detect and track treatment response, a screening tool is needed to identify patients for surgical evaluation and assess the quality of treatment. The identification of aberrant miRNA profiles in the sera of juvenile pilocytic astrocytoma patients could provide such a screening tool.

METHODS

The authors reviewed the serum profiles of 84 oncologically relevant miRNAs in pediatric juvenile pilocytic astrocytoma patients via qPCR screening.

RESULTS

miR-21, miR-15b, miR-23a, and miR-146b were significantly elevated in the sera of JPA patients as compared to non-oncologic controls, oncologic controls, and post-JPA resection samples (p < 0.001, 0.022, 0.034, 0.044). miR-21 had the highest AUC on ROC analysis (AUC > 0.99, sensitivity 75%, specificity 100%). All four miRNAs also correlated well with tumor mural nodule size, though they only poorly correlated with total tumor size, including cystic components (Spearman's R: miR-21 91.7 vs 6.9%, miR-15b 86.3 vs 23.1%, miR-23a 85.8 vs 23.0%, miR-146b 59.8 vs 11.9%).

CONCLUSION

In this small pilot study, pediatric juvenile pilocytic astrocytoma patients had significant elevations in serum miR-21, miR-15b, miR-23a, and miR-146b levels that do not appear to be driven by hydrocephalus or local distortion of the intracranial contents. These alterations correlate with solid tumor component volume and reverse with complete tumor resection, suggesting that this serum miRNA profile may delineate biomarkers for screening and tracking juvenile pilocytic astrocytoma patients. Additional studies, with a larger cohort, are needed to verify these results.

摘要

背景

青少年毛细胞型星形细胞瘤是儿童脑肿瘤中最大的一组。这些肿瘤的理想治疗方法是早期进行完全手术切除。为了检测和跟踪治疗反应,需要一种筛选工具来识别需要手术评估的患者,并评估治疗质量。青少年毛细胞型星形细胞瘤患者血清中异常 miRNA 谱的鉴定可能提供这样一种筛选工具。

方法

作者通过 qPCR 筛选,回顾性分析了 84 种与肿瘤相关的 miRNA 在儿科青少年毛细胞型星形细胞瘤患者血清中的谱型。

结果

与非肿瘤对照、肿瘤对照和青少年毛细胞型星形细胞瘤切除后样本相比,JPA 患者血清中的 miR-21、miR-15b、miR-23a 和 miR-146b 显著升高(p<0.001,0.022,0.034,0.044)。miR-21 在 ROC 分析中的 AUC 最高(AUC>0.99,敏感性 75%,特异性 100%)。虽然这四种 miRNA 与肿瘤壁结节大小相关性良好,但与总肿瘤大小(包括囊性成分)相关性较差(Spearman's R:miR-21 91.7%与 6.9%,miR-15b 86.3%与 23.1%,miR-23a 85.8%与 23.0%,miR-146b 59.8%与 11.9%)。

结论

在这项小型初步研究中,青少年毛细胞型星形细胞瘤患者血清中 miR-21、miR-15b、miR-23a 和 miR-146b 水平显著升高,这些升高似乎不是由脑积水或颅内内容物局部变形引起的。这些改变与实体瘤成分的体积相关,与完全肿瘤切除后逆转,提示这种血清 miRNA 谱可能描绘出筛查和跟踪青少年毛细胞型星形细胞瘤患者的生物标志物。需要进一步的研究,包括更大的队列,以验证这些结果。

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