Bookland Markus, Gillan Eileen, Song Xianyuan, Kolmakova Antonina
Divisions of1Neurosurgery and.
2Department of Pediatrics, University of Connecticut Health Center, Farmington; and.
J Neurosurg Pediatr. 2020 May 8;26(2):136-144. doi: 10.3171/2020.2.PEDS19715. Print 2020 Aug 1.
Micro RNAs (miRNAs) in peripheral biofluids (e.g., blood, saliva, urine) have been investigated as potential sources of diagnostic and prognostic information for a variety of tumor types, including pediatric brain tumors. While significant predictive associations have been identified between unique serum miRNA concentrations and some pediatric brain tumors, it is unclear whether serum miRNA abnormalities in pediatric brain tumor patients are representative of miRNA alterations in the tumor tissue compartment or whether they represent host tissue reactions to the presence of a brain tumor. The authors sought to identify whether serum miRNA changes in pediatric brain tumor patient sera could be explained by miRNA alterations within their tumors.
Matched serum and tissue samples were taken from a cohort of pediatric brain tumor patients (juvenile pilocytic astrocytoma [JPA] = 3, medulloblastoma = 4, ependymoma = 3), and unmatched control samples (n = 5) were acquired from control pediatric patients without oncological diagnoses. Extracted RNAs were tested within an array of 84 miRNAs previously noted to be relevant in a variety of brain tumors.
miR-26a-5p correlated strongly in JPA patients within both the serum and tumor tissue samples (R2 = 0.951, p = 0.046), and serum levels were highly predictive of JPA (area under the curve = 0.751, p = 0.027). No other miRNAs that were significantly correlated between biological compartments were significantly associated with brain tumor type. In total, 15 of 84 tested miRNAs in JPA patients, 14 of 84 tested miRNAs in ependymoma patients, and 4 of 84 tested miRNAs in medulloblastoma patients were significantly, positively correlated between serum and tumor tissue compartments (R2 > 0.950, p < 0.05).
The majority of miRNA changes in pediatric brain tumor patient sera that are significantly associated with the presence of a brain tumor do not correlate with brain tumor miRNA expression levels. This suggests that peripheral miRNA changes within pediatric brain tumor patients likely derive from tissues other than the tumors themselves.
外周生物流体（如血液、唾液、尿液）中的微小RNA（miRNA）已被研究作为多种肿瘤类型（包括小儿脑肿瘤）诊断和预后信息的潜在来源。虽然已确定独特的血清miRNA浓度与一些小儿脑肿瘤之间存在显著的预测关联，但尚不清楚小儿脑肿瘤患者血清中的miRNA异常是代表肿瘤组织区室中的miRNA改变，还是代表宿主组织对脑肿瘤存在的反应。作者试图确定小儿脑肿瘤患者血清中的miRNA变化是否可以由其肿瘤内的miRNA改变来解释。
从一组小儿脑肿瘤患者（青少年毛细胞型星形细胞瘤[JPA]=3例、髓母细胞瘤=4例、室管膜瘤=3例）中采集匹配的血清和组织样本，并从未经肿瘤诊断的对照小儿患者中获取不匹配的对照样本（n=5）。在先前已注意到与多种脑肿瘤相关的84种miRNA阵列中对提取的RNA进行检测。
miR-26a-5p在JPA患者的血清和肿瘤组织样本中均具有很强的相关性（R2 = 0.951，p = 0.046），血清水平对JPA具有高度预测性（曲线下面积 = 0.751，p = 0.027）。生物区室之间无其他显著相关的miRNA与脑肿瘤类型显著相关。总体而言，JPA患者中84种检测的miRNA中有15种、室管膜瘤患者中84种检测的miRNA中有14种、髓母细胞瘤患者中84种检测的miRNA中有4种在血清和肿瘤组织区室之间显著正相关（R2>0.950，p<0.05）。
小儿脑肿瘤患者血清中与脑肿瘤存在显著相关的大多数miRNA变化与脑肿瘤miRNA表达水平无关。这表明小儿脑肿瘤患者外周miRNA变化可能源自肿瘤本身以外的组织。
