基于血浆脂质组学技术探索儿童髓母细胞瘤转移的潜在生物标志物

杨春静; 续茜桥; 宝丽; 武万水; 姜德春; 时正媛

doi:10.7499/j.issn.1008-8830.2503030

PDF(810 KB)

HTML

中国当代儿科杂志 ›› 2025, Vol. 27 ›› Issue (11) : 1384-1390. DOI: 10.7499/j.issn.1008-8830.2503030

论著·临床研究

基于血浆脂质组学技术探索儿童髓母细胞瘤转移的潜在生物标志物

杨春静 ¹ ,
续茜桥 ¹ ,
宝丽 ¹ ,
武万水 ² ,
姜德春 ¹ ,
时正媛 ¹

作者信息 +

Plasma lipidomics-based exploration of potential biomarkers of metastasis in pediatric medulloblastoma

Author information +

文章历史 +

摘要

目的通过脂质组学探讨区分髓母细胞瘤（medulloblastoma, MB）中，非转移MB（non-metastatic MB, nmMB）和转移MB（metastatic MB, mMB）患儿的潜在生物标志物。方法该文为前瞻性研究，选取17例mMB患儿和20例与之匹配的nmMB患儿。采集mMB和nmMB患儿血浆样本，使用超高效液相色谱-四极杆飞行时间质谱的方法检测脂类的血浆代谢物，并分析其相关性及诊断价值。结果通过脂质轮廓构建的正交偏最小二乘判别分析模型，在nmMB组和mMB组患儿血浆中共筛选出14种差异脂质，包括二酰基甘油DG（18:2/20:4/0:0）、鞘磷脂SM（d18:1/20:0）等。受试者操作特征曲线分析显示有9种代谢标志物的曲线下面积大于0.7。差异脂质富集于鞘脂代谢、甘油磷脂代谢、花生四烯酸代谢，提示其与转移表型相关。结论脂质组学呈现了一种针对mMB的新的识别方法，鉴定的脂质代谢物可为mMB的早期诊治、预后评估和药物治疗靶点的选择提供支持和依据。

Abstract

Objective To identify potential plasma lipidomic biomarkers that distinguish non-metastatic medulloblastoma (nmMB) from metastatic medulloblastoma (mMB) in children. Methods In this prospective study, 17 children with mMB and 20 matched children with nmMB were enrolled. Plasma samples were analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Lipid metabolites were evaluated for their associations and diagnostic performance. Results Orthogonal partial least squares discriminant analysis based on lipid profiles clearly separated nmMB from mMB, and 14 differential lipids were identified, including DG(18:2/20:4/0:0) and SM(d18:1/20:0). Receiver operating characteristic analysis showed nine metabolites with area under the curve greater than 0.7. Differential lipids were enriched in sphingolipid, glycerophospholipid, and arachidonic acid metabolism, suggesting an association with the metastatic phenotype. Conclusions Plasma lipidomics provides a new approach to identify mMB, and the identified lipid metabolites may support early diagnosis and treatment, prognostic assessment, and selection of therapeutic targets for metastatic medulloblastoma.

导出引用

杨春静, 续茜桥, 宝丽, 等. 基于血浆脂质组学技术探索儿童髓母细胞瘤转移的潜在生物标志物[J]. 中国当代儿科杂志. 2025, 27(11): 1384-1390 https://doi.org/10.7499/j.issn.1008-8830.2503030

Chun-Jing YANG, Xi-Qiao XU, Li BAO, et al. Plasma lipidomics-based exploration of potential biomarkers of metastasis in pediatric medulloblastoma[J]. Chinese Journal of Contemporary Pediatrics. 2025, 27(11): 1384-1390 https://doi.org/10.7499/j.issn.1008-8830.2503030

参考文献

列表( 原文顺序 | 文献年度倒序 | 文中引用次数倒序 ) 可视化分析

[1]

Bautista

, Fioravantti

, de Rojas

, et al. Medulloblastoma in children and adolescents: a systematic review of contemporary phase I and II clinical trials and biology update[J]. Cancer Med, 2017, 6(11): 2606-2624. PMCID: PMC5673921. DOI: 10.1002/cam4.1171 .

https://www.ncbi.nlm.nih.gov/pubmed/28980418

本文引用 [1]

[2]	Rolland A, Aquilina K. Surgery for recurrent medulloblastoma: a review[J]. Neurochirurgie, 2021, 67(1): 69-75. DOI: 10.1016/j.neuchi.2019.06.008 . https://www.ncbi.nlm.nih.gov/pubmed/31351079 本文引用 [1]

[3]	Li M, Deng Y, Zhang W. Molecular determinants of medulloblastoma metastasis and leptomeningeal dissemination[J]. Mol Cancer Res, 2021, 19(5): 743-752. DOI: 10.1158/1541-7786.MCR-20-1026 . https://www.ncbi.nlm.nih.gov/pubmed/33608450 本文引用 [1]

[4]	Wang R, Li B, Lam SM, et al. Integration of lipidomics and metabolomics for in-depth understanding of cellular mechanism and disease progression[J]. J Genet Genomics, 2020, 47(2): 69-83. DOI: 10.1016/j.jgg.2019.11.009 . https://www.ncbi.nlm.nih.gov/pubmed/32178981 本文引用 [1]

[5]	Martin-Perez M, Urdiroz-Urricelqui U, Bigas C, et al. The role of lipids in cancer progression and metastasis[J]. Cell Metab, 2022, 34(11): 1675-1699. DOI: 10.1016/j.cmet.2022.09.023 . https://www.ncbi.nlm.nih.gov/pubmed/36261043 本文引用 [2]

[6]	Viswanathan VS, Ryan MJ, Dhruv HD, et al. Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway[J]. Nature, 2017, 547(7664): 453-457. PMCID: PMC5667900. DOI: 10.1038/nature23007 . https://www.ncbi.nlm.nih.gov/pubmed/28678785

[7]	Gong J, Lin Y, Zhang H, et al. Reprogramming of lipid metabolism in cancer-associated fibroblasts potentiates migration of colorectal cancer cells[J]. Cell Death Dis, 2020, 11(4): 267. PMCID: PMC7181758. DOI: 10.1038/s41419-020-2434-z . https://www.ncbi.nlm.nih.gov/pubmed/32327627

[8]	Jarmusch AK, Pirro V, Baird Z, et al. Lipid and metabolite profiles of human brain tumors by desorption electrospray ionization-MS[J]. Proc Natl Acad Sci U S A, 2016, 113(6): 1486-1491. PMCID: PMC4760779. DOI: 10.1073/pnas.1523306113 . https://www.ncbi.nlm.nih.gov/pubmed/26787885

[9]	尤铂文, 单军奇, 姚瑶, 等. 血浆代谢相关生物标志物检测在转移性结直肠癌诊断中的应用[J]. 中华肿瘤防治杂志, 2024, 31(7): 420-425. DOI: 10.16073/j.cnki.cjcpt.2024.07.05 . 本文引用 [1]

[10]	Wang Y. Applications of lipidomics in tumor diagnosis and therapy[J]. Adv Exp Med Biol, 2021, 1316: 25-39. DOI: 10.1007/978-981-33-6785-2_2 . https://www.ncbi.nlm.nih.gov/pubmed/33740241 本文引用 [1]

[11]	Bergers G, Fendt SM. The metabolism of cancer cells during metastasis[J]. Nat Rev Cancer, 2021, 21(3): 162-180. PMCID: PMC8733955. DOI: 10.1038/s41568-020-00320-2 . https://www.ncbi.nlm.nih.gov/pubmed/33462499 本文引用 [1]

[12]	Paine MRL, Liu J, Huang D, et al. Three-dimensional mass spectrometry imaging identifies lipid markers of medulloblastoma metastasis[J]. Sci Rep, 2019, 9(1): 2205. PMCID: PMC6379434. DOI: 10.1038/s41598-018-38257-0 . https://www.ncbi.nlm.nih.gov/pubmed/30778099 本文引用 [1]

[13]	Stoica C, Ferreira AK, Hannan K, et al. Bilayer forming phospholipids as targets for cancer therapy[J]. Int J Mol Sci, 2022, 23(9): 5266. PMCID: PMC9100777. DOI: 10.3390/ijms23095266 . https://www.ncbi.nlm.nih.gov/pubmed/35563655 本文引用 [1]

[14]	Lima LG, Chammas R, Monteiro RQ, et al. Tumor-derived microvesicles modulate the establishment of metastatic melanoma in a phosphatidylserine-dependent manner[J]. Cancer Lett, 2009, 283(2): 168-175. DOI: 10.1016/j.canlet.2009.03.041 . https://www.ncbi.nlm.nih.gov/pubmed/19401262 本文引用 [1]

[15]

Jantscheff

, Schlesinger

, Fritzsche

, et al. Lysophosphatidylcholine pretreatment reduces VLA-4 and P-selectin-mediated b16.f10 melanoma cell adhesion in vitro and inhibits metastasis-like lung invasion in vivo [J]. Mol Cancer Ther, 2011, 10(1): 186-197. DOI: 10.1158/1535-7163.MCT-10-0474 .

https://www.ncbi.nlm.nih.gov/pubmed/21220501

本文引用 [1]

[16]

Zhang

, Liu

, et al. Lysophosphatidylcholine inhibits lung cancer cell proliferation by regulating fatty acid metabolism enzyme long-chain acyl-coenzyme A synthase 5[J]. Clin Transl Med, 2023, 13(1): e1180. PMCID: PMC9839868. DOI: 10.1002/ctm2.1180 .

https://www.ncbi.nlm.nih.gov/pubmed/36639836

本文引用 [1]

[17]

Zheng

, Chen

, Feng

, et al. Sphingomyelin synthase 2 promotes an aggressive breast cancer phenotype by disrupting the homoeostasis of ceramide and sphingomyelin[J]. Cell Death Dis, 2019, 10(3): 157. PMCID: PMC6377618. DOI: 10.1038/s41419-019-1303-0 .

https://www.ncbi.nlm.nih.gov/pubmed/30770781

本文引用 [1]

[18]	van Mastrigt E, Zweekhorst S, Bol B, et al. Ceramides in tracheal aspirates of preterm infants: marker for bronchopulmonary dysplasia[J]. PLoS One, 2018, 13(1): e0185969. PMCID: PMC5773003. DOI: 10.1371/journal.pone.0185969 . https://www.ncbi.nlm.nih.gov/pubmed/29346372 本文引用 [1]

[19]

Zhou

, Huang

, Ma

, et al. Dysregulated ceramides metabolism by fatty acid 2-hydroxylase exposes a metabolic vulnerability to target cancer metastasis[J]. Signal Transduct Target Ther, 2022, 7(1): 370. PMCID: PMC9588768. DOI: 10.1038/s41392-022-01199-1 .

https://www.ncbi.nlm.nih.gov/pubmed/36274060

本文引用 [1]

[20]

Shen

, Liu

, Hu

, et al. Single-cell RNA sequencing reveals aberrant sphingolipid metabolism in non-small cell lung cancer impacts tumor-associated macrophages and stimulates angiogenesis via macrophage inhibitory factor signaling[J]. Thorac Cancer, 2024, 15(14): 1164-1175. PMCID: PMC11091791. DOI: 10.1111/1759-7714.15283 .

https://www.ncbi.nlm.nih.gov/pubmed/38587042

本文引用 [1]

[21]	Kuo A, Hla T. Regulation of cellular and systemic sphingolipid homeostasis[J]. Nat Rev Mol Cell Biol, 2024, 25(10): 802-821. PMCID: PMC12034107. DOI: 10.1038/s41580-024-00742-y . https://www.ncbi.nlm.nih.gov/pubmed/38890457 本文引用 [1]

[22]	Yin B, Yang Y, Zhao Z, et al. Arachidonate 12-lipoxygenase may serve as a potential marker and therapeutic target for prostate cancer stem cells[J]. Int J Oncol, 2011, 38(4): 1041-1046. PMCID: PMC4560359. DOI: 10.3892/ijo.2011.901 . https://www.ncbi.nlm.nih.gov/pubmed/21225230 本文引用 [1]