Proteomic analysis of cerebrospinal fluid from children with central nervous system tumors identifies candidate proteins relating to tumor metastatic spread.
Proteomic analysis of cerebrospinal fluid from children with central nervous system tumors identifies candidate proteins relating to tumor metastatic spread.
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DOI：
10.18632/oncotarget.17579
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发表时间：
2017-07-11
期刊：
影响因子：
--
通讯作者：
Massimino M
中科院分区：
文献类型：
--
作者：
Spreafico F;Bongarzone I;Pizzamiglio S;Magni R;Taverna E;De Bortoli M;Ciniselli CM;Barzanò E;Biassoni V;Luchini A;Liotta LA;Zhou W;Signore M;Verderio P;Massimino M
中枢神经系统（CNS）肿瘤是儿童最常见的实体肿瘤。由于联合脑脊液（CSF）细胞学和放射神经影像学检测脑膜转移的敏感性仍然相对较低，我们试图表征CSF肿瘤患者的CSF蛋白质组，以确定预测转移性扩散的生物标志物。使用核-壳水凝胶纳米颗粒处理来自27名患有脑肿瘤的儿童和13名对照（CNS外非霍奇金淋巴瘤）的CSF样本，并使用反相液相色谱/电喷雾串联质谱（LC-MS/MS）进行分析。用Fisher精确检验和/或单变量逻辑回归模型鉴定候选蛋白质。在训练集和一组独立的CFS样本（60例，14例对照）中使用反相蛋白阵列（RPPA），蛋白质印迹（WB）和ELISA来验证我们的发现。在通过LC-MS/MS鉴定的558个非冗余蛋白质中，147个从http://www.biosino.org的CSF数据库中缺失。选择26个最终的最佳候选蛋白质中的14个用于WB、RPPA和ELISA方法的验证。6种蛋白质（1型胶原、胰岛素样生长因子结合蛋白4、前胶原C-内肽酶增强子1、胶质细胞系衍生的神经营养因子受体α2、间α-胰蛋白酶抑制剂重链4、神经增殖和分化控制蛋白-1）显示了区分转移病例与对照的能力。将来自儿科CNS肿瘤的CSF的独特数据集与一种新的使能纳米技术相结合，使我们能够鉴定出可能与转移状态相关的CSF蛋白。
Central nervous system (CNS) tumors are the most common solid tumors in childhood. Since the sensitivity of combined cerebrospinal fluid (CSF) cytology and radiological neuroimaging in detecting meningeal metastases remains relatively low, we sought to characterize the CSF proteome of patients with CSF tumors to identify biomarkers predictive of metastatic spread. CSF samples from 27 children with brain tumors and 13 controls (extra-CNS non-Hodgkin lymphoma) were processed using core-shell hydrogel nanoparticles, and analyzed with reverse-phase liquid chromatography/electrospray tandem mass spectrometry (LC-MS/MS). Candidate proteins were identified with Fisher's exact test and/or a univariate logistic regression model. Reverse phase protein array (RPPA), Western blot (WB), and ELISA were used in the training set and in an independent set of CFS samples (60 cases, 14 controls) to validate our discovery findings. Among the 558 non-redundant proteins identified by LC-MS/MS, 147 were missing from the CSF database at http://www.biosino.org. Fourteen of the 26 final top-candidate proteins were chosen for validation with WB, RPPA and ELISA methods. Six proteins (type 1 collagen, insulin-like growth factor binding protein 4, procollagen C-endopeptidase enhancer 1, glial cell-line derived neurotrophic factor receptor α2, inter-alpha-trypsin inhibitor heavy chain 4, neural proliferation and differentiation control protein-1) revealed the ability to discriminate metastatic cases from controls. Combining a unique dataset of CSFs from pediatric CNS tumors with a novel enabling nanotechnology led us to identify CSF proteins potentially related to metastatic status.
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影响因子：
5.1
作者：
Lecolle, K.;Begard, S.;Colin, M.
通讯作者：
Colin, M.
影响因子：
3.4
作者：
Conti, Amalia;Fredolini, Claudia;Benassi, Maria Serena
通讯作者：
Benassi, Maria Serena
影响因子：
14.9
作者：
Li SJ;Peng M;Li H;Liu BS;Wang C;Wu JR;Li YX;Zeng R
通讯作者：
Zeng R
影响因子：
3.7
作者：
Hölttä M;Zetterberg H;Mirgorodskaya E;Mattsson N;Blennow K;Gobom J
通讯作者：
Gobom J
影响因子：
3.8
作者：
Mathioudakis, Nestoras;Sundaresh, Ram;Larsen, Alexandra;Ruff, William;Schiller, Jennifer;Guerrero-Cazares, Hugo;Burger, Peter;Salvatori, Roberto;Quinones-Hinojosa, Alfredo
通讯作者：
Quinones-Hinojosa, Alfredo