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General Research Article

蛋白质组学分析揭示了小儿脑积水的功能途径和潜在靶点

卷 23, 期 5, 2023

发表于: 03 July, 2023

页: [400 - 409] 页: 10

弟呕挨: 10.2174/1566523223666230613144056

价格: $65

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摘要

简介：脑积水是一种常见的小儿脑脊液生理学疾病，导致脑室异常扩张。然而，潜在的分子机制仍然未知。 方法：我们对 7 名先天性脑积水和 5 名接受手术治疗的蛛网膜囊肿患者的脑脊液 (CSF) 进行了蛋白质组学分析。通过无标记质谱法鉴定差异表达蛋白（DEP），然后进行差异表达分析。进行 GO 和 GSEA 富集分析以探索受 DEP 影响的癌症标志通路和免疫相关通路。然后，应用网络分析揭示 DEP 在人类蛋白质-蛋白质相互作用 (PPI) 网络中的位置。根据药物与靶标的相互作用，确定了治疗脑积水的潜在药物。 结果：我们鉴定了 148 个上调蛋白和 82 个下调蛋白，它们是临床诊断脑积水和蛛网膜囊肿的潜在生物标志物。功能富集分析显示，DEP 在癌症标志通路和免疫相关通路中显着富集。此外，网络分析发现DEP更有可能位于人类PPI网络的中心区域，这表明DEP可能是在人类PPI中发挥重要作用的蛋白质。最后，我们计算了药物靶点的重叠度和基于药物靶点相互作用的DEP，以确定脑积水的潜在治疗药物。 结论：全面的蛋白质组学分析为研究脑积水的分子通路提供了宝贵的资源，并发现了临床诊断和治疗的潜在生物标志物

关键词: 蛋白质组，小儿脑积水，分子途径，DEP，蛋白质，药物。

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[1]
Kahle KT, Kulkarni AV, Limbrick DD Jr, Warf BC. Hydrocephalus in children. Lancet 2016; 387(10020): 788-99.
[http://dx.doi.org/10.1016/S0140-6736(15)60694-8] [PMID: 26256071]
[2]
Simon TD, Riva-Cambrin J, Srivastava R, Bratton SL, Dean JM, Kestle JR. Hospital care for children with hydrocephalus in the United States: Utilization, charges, comorbidities, and deaths. J Neurosurg Pediatr 2008; 1(2): 131-7.
[http://dx.doi.org/10.3171/PED/2008/1/2/131] [PMID: 18352782]
[3]
Tully HM, Dobyns WB. Infantile hydrocephalus: A review of epidemiology, classification and causes. Eur J Med Genet 2014; 57(8): 359-68.
[http://dx.doi.org/10.1016/j.ejmg.2014.06.002] [PMID: 24932902]
[4]
Gelabert-González M. (Intracranial arachnoid cysts). Rev Neurol 2004; 39(12): 1161-6.
[PMID: 15625636]
[5]
Westermaier T, Schweitzer T, Ernestus RI. Arachnoid Cysts. Adv Exp Med Biol 2012; 724: 37-50.
[http://dx.doi.org/10.1007/978-1-4614-0653-2_3] [PMID: 22411232]
[6]
Hall S, Smedley A, Sparrow O, et al. Natural history of Intracranial Arachnoid Cysts. World Neurosurg 2019; 126: e1315-20.
[http://dx.doi.org/10.1016/j.wneu.2019.03.087] [PMID: 30898748]
[7]
Mustansir F, Bashir S, Darbar A. Management of arachnoid cysts: A comprehensive review. Cureus 2018; 10(4): e2458.
[http://dx.doi.org/10.7759/cureus.2458] [PMID: 29888162]
[8]
Hochstetler A, Raskin J, Blazer-Yost BL. Hydrocephalus: Historical analysis and considerations for treatment. Eur J Med Res 2022; 27(1): 168.
[http://dx.doi.org/10.1186/s40001-022-00798-6] [PMID: 36050779]
[9]
Garcia-Bonilla M, McAllister J, Limbrick D. Genetics and molecular pathogenesis of human hydrocephalus. Neurol India 2021; 69(8) (Suppl.): 268.
[http://dx.doi.org/10.4103/0028-3886.332249] [PMID: 35102976]
[10]
McAllister JP II. Pathophysiology of congenital and neonatal hydrocephalus. Semin Fetal Neonatal Med 2012; 17(5): 285-94.
[http://dx.doi.org/10.1016/j.siny.2012.06.004] [PMID: 22800608]
[11]
Ren P, Wang J, Li L, et al. Identification of key genes involved in the recurrence of glioblastoma multiforme using weighted gene co-expression network analysis and differential expression analysis. Bioengineered 2021; 12(1): 3188-200.
[http://dx.doi.org/10.1080/21655979.2021.1943986] [PMID: 34238116]
[12]
Soneson C, Robinson MD. Bias, robustness and scalability in single-cell differential expression analysis. Nat Methods 2018; 15(4): 255-61.
[http://dx.doi.org/10.1038/nmeth.4612] [PMID: 29481549]
[13]
Hu JG, Fu SL, Zhang KH, et al. Differential gene expression in neural stem cells and oligodendrocyte precursor cells: A cDNA microarray analysis. J Neurosci Res 2004; 78(5): 637-46.
[http://dx.doi.org/10.1002/jnr.20317] [PMID: 15499592]
[14]
Hua XF, Wang XB, Liu FJ. Functional analysis of human cancer-associated genes and their association with the testes and epididymis. Oncol Lett 2013; 6(3): 811-6.
[http://dx.doi.org/10.3892/ol.2013.1450] [PMID: 24137416]
[15]
Yu G, Wang LG, Han Y, He QY. ClusterProfiler: An R package for comparing biological themes among gene clusters. OMICS 2012; 16(5): 284-7.
[http://dx.doi.org/10.1089/omi.2011.0118] [PMID: 22455463]
[16]
Kolberg L, Raudvere U, Kuzmin I, Vilo J, Peterson H. gprofiler2 -- an R package for gene list functional enrichment analysis and namespace conversion toolset g: Profiler. F1000 Res 2020; 9.
[17]
Jallo GI, Woo HH, Meshki C, Epstein FJ, Wisoff JH. Arachnoid cysts of the cerebellopontine angle: Diagnosis and surgery. Neurosurgery 1997; 40(1): 31-7.
[PMID: 8971821]
[18]
González GL, Ros-López B, Ibáñez-Botella G, Romero ML, Martin GA, Arráez-Sánchez MÁ. Neuroendoscopic treatment for hydrocephalus associated to midline arachnoid cysts in a series of nine pediatric patients. Minerva Pediatr 2017; 69(4): 256-63.
[PMID: 26041004]
[19]
Cincu R, Agrawal A, Eiras J. Intracranial arachnoid cysts: Current concepts and treatment alternatives. Clin Neurol Neurosurg 2007; 109(10): 837-43.
[http://dx.doi.org/10.1016/j.clineuro.2007.07.013] [PMID: 17764831]
[20]
Karimy JK, Reeves BC, Damisah E, et al. Inflammation in acquired hydrocephalus: Pathogenic mechanisms and therapeutic targets. Nat Rev Neurol 2020; 16(5): 285-96.
[http://dx.doi.org/10.1038/s41582-020-0321-y] [PMID: 32152460]
[21]
Pandey S, Yao PW, Qian Z, Ji T, Wang K, Gao L. Clinical characteristics of hydrocephalus following the treatment of pyogenic ventriculitis caused by multi/extensive Drug-Resistant Gram-Negative Bacilli, Acinetobacter Baumannii, and Klebsiella Pneumoniae. Front Surg 2022; 9: 854627.
[http://dx.doi.org/10.3389/fsurg.2022.854627] [PMID: 35592123]
[22]
Wang X, Zhou Y, Wang J, et al. SNX27 deletion causes hydrocephalus by impairing ependymal cell differentiation and ciliogenesis. J Neurosci 2016; 36(50): 12586-97.
[http://dx.doi.org/10.1523/JNEUROSCI.1620-16.2016] [PMID: 27974614]
[23]
Zhou Y, Hou Y, Shen J, Huang Y, Martin W, Cheng F. Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov 2020; 6(1): 14.
[http://dx.doi.org/10.1038/s41421-020-0153-3] [PMID: 32194980]
[24]
Lu Y, Yuan L, Chen X, Zhang A, Zhang P, Zou D. Systematic analysis and identification of unexpected interactions from the neuroprotein drug interactome in hydrocephalus pharmacological intervention. J Bioinform Comput Biol 2019; 17(1): 1950002.
[http://dx.doi.org/10.1142/S0219720019500021] [PMID: 30866733]
[25]
Tyanova S, Temu T, Cox J. The MaxQuant computational platform for mass spectrometry-based shotgun proteomics. Nat Protoc 2016; 11(12): 2301-19.
[http://dx.doi.org/10.1038/nprot.2016.136] [PMID: 27809316]
[26]
The Gene Ontology Consortium. Going forward. Nucleic Acids Res 2015; 43(D1): D1049-56.
[http://dx.doi.org/10.1093/nar/gku1179] [PMID: 25428369]
[27]
Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 2005; 102(43): 15545-50.
[http://dx.doi.org/10.1073/pnas.0506580102] [PMID: 16199517]
[28]
Liberzon A, Birger C, Thorvaldsdóttir H, Ghandi M, Mesirov JP, Tamayo P. The molecular signatures database (MSigDB) hallmark gene set collection. Cell Syst 2015; 1(6): 417-25.
[http://dx.doi.org/10.1016/j.cels.2015.12.004] [PMID: 26771021]
[29]
Zou H, Pan T, Gao Y, et al. Pan-cancer assessment of mutational landscape in intrinsically disordered hotspots reveals potential driver genes. Nucleic Acids Res 2022; 50(9): e49.
[PMID: 35061901]
[30]
Wishart DS, Feunang YD, Guo AC, et al. DrugBank 5.0: A major update to the DrugBank database for 2018. Nucleic Acids Res 2018; 46(D1): D1074-82.
[http://dx.doi.org/10.1093/nar/gkx1037] [PMID: 29126136]
[31]
Shima Y, Copeland NG, Gilbert DJ, et al. Differential expression of the seven-pass transmembrane cadherin genesCelsr1-3 and distribution of the Celsr2 protein during mouse development. Dev Dyn 2002; 223(3): 321-32.
[http://dx.doi.org/10.1002/dvdy.10054] [PMID: 11891983]
[32]
Huber C, Cormier-Daire V. Ciliary disorder of the skeleton. Am J Med Genet C Semin Med Genet 2012; 160C(3): 165-74.
[http://dx.doi.org/10.1002/ajmg.c.31336] [PMID: 22791528]
[33]
Tissir F, Qu Y, Montcouquiol M, et al. Lack of cadherins Celsr2 and Celsr3 impairs ependymal ciliogenesis, leading to fatal hydrocephalus. Nat Neurosci 2010; 13(6): 700-7.
[http://dx.doi.org/10.1038/nn.2555] [PMID: 20473291]
[34]
Greig FH, Nixon GF. Phosphoprotein enriched in astrocytes (PEA)-15: A potential therapeutic target in multiple disease states. Pharmacol Ther 2014; 143(3): 265-74.
[http://dx.doi.org/10.1016/j.pharmthera.2014.03.006] [PMID: 24657708]
[35]
Xiao M, Li J, Liu Q, He X, Yang Z, Wang D. Expression and role of TRIM2 in human diseases. BioMed Res Int 2022; 2022: 1-14.
[http://dx.doi.org/10.1155/2022/9430509] [PMID: 36051486]
[36]
Li Y, Jiang T, Zhou W, et al. Pan-cancer characterization of immune-related lncRNAs identifies potential oncogenic biomarkers. Nat Commun 2020; 11(1): 1000.
[http://dx.doi.org/10.1038/s41467-020-14802-2] [PMID: 32081859]
[37]
Bhattacharya S, Dunn P, Thomas CG, et al. ImmPort, toward repurposing of open access immunological assay data for translational and clinical research. Sci Data 2018; 5(1): 180015.
[http://dx.doi.org/10.1038/sdata.2018.15] [PMID: 29485622]
[38]
Goh KI, Cusick ME, Valle D, Childs B, Vidal M, Barabási AL. The human disease network. Proc Natl Acad Sci 2007; 104(21): 8685-90.
[http://dx.doi.org/10.1073/pnas.0701361104] [PMID: 17502601]
[39]
Barrat A, Barthélemy M, Pastor-Satorras R, Vespignani A. The architecture of complex weighted networks. Proc Natl Acad Sci 2004; 101(11): 3747-52.
[http://dx.doi.org/10.1073/pnas.0400087101] [PMID: 15007165]
[40]
Linares TJ, Ros LB, Iglesias MS, Ibáñez BG, Ros SÁ, Arráez SMÁ. Neuroendoscopic treatment of arachnoid cysts in the paediatric population. Series results for 20 patients. Neurocirugia 2020; 31(4): 165-72.
[http://dx.doi.org/10.1016/j.neucie.2020.02.002] [PMID: 31883710]
[41]
Akgun B, Ozturk S, Hergunsel OB, Erol FS, Demir F. Endoscopic third ventriculostomy for obstructive hydrocephalus and ventriculocystostomy for intraventricular arachnoid cysts. Acta Med 2021; 64(1): 29-35.
[http://dx.doi.org/10.14712/18059694.2021.5] [PMID: 33855956]
[42]
Verkman AS, Tradtrantip L, Smith AJ, Yao X. Aquaporin water channels and hydrocephalus. Pediatr Neurosurg 2017; 52(6): 409-16.
[http://dx.doi.org/10.1159/000452168] [PMID: 27978530]
[43]
Ahluwalia P, Mondal AK, Bloomer C, et al. Identification and clinical validation of a novel 4 Gene-Signature with prognostic utility in colorectal cancer. Int J Mol Sci 2019; 20(15): 3818.
[http://dx.doi.org/10.3390/ijms20153818] [PMID: 31387239]
[44]
Hu X, Bao M, Huang J, Zhou L, Zheng S. Corrigendum: Identification and validation of novel biomarkers for diagnosis and prognosis of hepatocellular carcinoma. Front Oncol 2020; 10: 617539.
[http://dx.doi.org/10.3389/fonc.2020.617539] [PMID: 33330112]
[45]
Baharudin R, Tieng FYF, Lee LH, Ab Mutalib NS. Epigenetics of SFRP1: The dual roles in human cancers. Cancers 2020; 12(2): 445.
[http://dx.doi.org/10.3390/cancers12020445] [PMID: 32074995]
[46]
Bernemann C, Hülsewig C, Ruckert C, et al. Influence of secreted frizzled receptor protein 1 (SFRP1) on neoadjuvant chemotherapy in triple negative breast cancer does not rely on WNT signaling. Mol Cancer 2014; 13(1): 174.
[http://dx.doi.org/10.1186/1476-4598-13-174] [PMID: 25033833]
[47]
Jeong YJ, Jeong HY, Bong JG, Park SH, Oh HK. Low methylation levels of the SFRP1 gene are associated with the basal-like subtype of breast cancer. Oncol Rep 2013; 29(5): 1946-54.
[http://dx.doi.org/10.3892/or.2013.2335] [PMID: 23467623]
[48]
Lin H, Yang G, Ding B, et al. Secreted frizzled-related protein 1 overexpression in gastric cancer: Relationship with radiological findings of dual-energy spectral CT and PET-CT. Sci Rep 2017; 7(1): 42020.
[http://dx.doi.org/10.1038/srep42020] [PMID: 28169332]
[49]
Qu Y, Ray PS, Li J, et al. High levels of secreted frizzled-related protein 1 correlate with poor prognosis and promote tumourigenesis in gastric cancer. Eur J Cancer 2013; 49(17): 3718-28.
[50]
Saini S, Liu J, Yamamura S, et al. Functional significance of secreted Frizzled-related protein 1 in metastatic renal cell carcinomas. Cancer Res 2009; 69(17): 6815-22.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-1254] [PMID: 19723665]
[51]
van der Linden M, Meyaard L. Fine-tuning neutrophil activation: Strategies and consequences. Immunol Lett 2016; 178: 3-9.
[http://dx.doi.org/10.1016/j.imlet.2016.05.015] [PMID: 27262927]
[52]
Niyaz M, Khan MS, Mudassar S. Hedgehog signaling: An achilles’ heel in cancer. Transl Oncol 2019; 12(10): 1334-44.
[http://dx.doi.org/10.1016/j.tranon.2019.07.004] [PMID: 31352196]
[53]
Skoda AM, Simovic D, Karin V, Kardum V, Vranic S, Serman L. The role of the Hedgehog signaling pathway in cancer: A comprehensive review. Bosn J Basic Med Sci 2018; 18(1): 8-20.
[http://dx.doi.org/10.17305/bjbms.2018.2756] [PMID: 29274272]
[54]
Crescioli C. Chemokines and transplant outcome. Clin Biochem 2016; 49(4-5): 355-62.
[http://dx.doi.org/10.1016/j.clinbiochem.2015.07.026] [PMID: 26238260]

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