Identification of metabolite biomarkers for pancreatic neuroendocrine tumours using a metabolomic approach.

IF 5.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Arnaud Jannin, Sophie Dabo-Niang, Christine Do Cao, Amandine Descat, Stéphanie Espiard, Catherine Cardot-Bauters, Marie-Christine Vantyghem, Benjamin Chevalier, Jean François Goossens, Benjamin Marsac, Jimmy Vandel, Sophie Dominguez, Robert Caiazzo, François Pattou, Camille Marciniak, Medhi El Amrani, Isabelle Van Seuningen, Nicolas Jonckheere, Anne-Frédérique Dessein, Lucie Coppin
{"title":"Identification of metabolite biomarkers for pancreatic neuroendocrine tumours using a metabolomic approach.","authors":"Arnaud Jannin, Sophie Dabo-Niang, Christine Do Cao, Amandine Descat, Stéphanie Espiard, Catherine Cardot-Bauters, Marie-Christine Vantyghem, Benjamin Chevalier, Jean François Goossens, Benjamin Marsac, Jimmy Vandel, Sophie Dominguez, Robert Caiazzo, François Pattou, Camille Marciniak, Medhi El Amrani, Isabelle Van Seuningen, Nicolas Jonckheere, Anne-Frédérique Dessein, Lucie Coppin","doi":"10.1093/ejendo/lvaf055","DOIUrl":null,"url":null,"abstract":"<p><strong>Importance: </strong>Metabolic flexibility, a key hallmark of cancer, reflects aberrant tumour changes associated with metabolites. The metabolic plasticity of pancreatic neuroendocrine tumours (pNETs) remains largely unexplored. Notably, the heterogeneity of pNETs complicates their diagnosis, prognosis, and therapeutic management.</p><p><strong>Objective: </strong>Here, we compared the plasma metabolomic profiles of patients with pNET and non-cancerous individuals to understand metabolic dysregulation.</p><p><strong>Design, setting, participants, intervention and measure: </strong>Plasma metabolic profiles of 76 patients with pNETs and 38 non-cancerous individuals were analyzed using LC-MS/MS and FIA-MS/MS (Biocrates AbsoluteIDQ p180 kit). Statistical analyses, including univariate and multivariate methods, were performed along with the generation of receiver operating characteristic (ROC) curves for metabolomic signature identification.</p><p><strong>Results: </strong>Compared with non-cancerous individuals, patients with pNET exhibited elevated levels of phosphoglyceride metabolites and reduced acylcarnitine levels, indicating an upregulation of fatty acid oxidation (FAO), which is crucial for the energy metabolism of pNET cells and one-carbon metabolism metabolites. Elevated glutamate levels and decreased lipid metabolite levels have been observed in patients with metastatic pNETs. Patients with the germline MEN1 mutations showed lower amino acid metabolites and FAO, with increased metabolites related to leucine catabolism and lipid metabolism, compared to non-MEN1 mutated patients. The highest area under the ROC curve was observed in patients with pNET harbouring MEN1 mutations.</p><p><strong>Conclusion and relevance: </strong>This study highlights the distinct plasma metabolic signatures of pNETs, including the critical role of FAO and elevated glutamate levels in metastasis, supporting the energy and biosynthetic needs of rapidly proliferating tumour cells. Mapping of these dysregulated metabolites may facilitate the identification of new therapeutic targets for pNETs management.</p>","PeriodicalId":11884,"journal":{"name":"European Journal of Endocrinology","volume":" ","pages":"466-480"},"PeriodicalIF":5.3000,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Endocrinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/ejendo/lvaf055","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0

Abstract

Importance: Metabolic flexibility, a key hallmark of cancer, reflects aberrant tumour changes associated with metabolites. The metabolic plasticity of pancreatic neuroendocrine tumours (pNETs) remains largely unexplored. Notably, the heterogeneity of pNETs complicates their diagnosis, prognosis, and therapeutic management.

Objective: Here, we compared the plasma metabolomic profiles of patients with pNET and non-cancerous individuals to understand metabolic dysregulation.

Design, setting, participants, intervention and measure: Plasma metabolic profiles of 76 patients with pNETs and 38 non-cancerous individuals were analyzed using LC-MS/MS and FIA-MS/MS (Biocrates AbsoluteIDQ p180 kit). Statistical analyses, including univariate and multivariate methods, were performed along with the generation of receiver operating characteristic (ROC) curves for metabolomic signature identification.

Results: Compared with non-cancerous individuals, patients with pNET exhibited elevated levels of phosphoglyceride metabolites and reduced acylcarnitine levels, indicating an upregulation of fatty acid oxidation (FAO), which is crucial for the energy metabolism of pNET cells and one-carbon metabolism metabolites. Elevated glutamate levels and decreased lipid metabolite levels have been observed in patients with metastatic pNETs. Patients with the germline MEN1 mutations showed lower amino acid metabolites and FAO, with increased metabolites related to leucine catabolism and lipid metabolism, compared to non-MEN1 mutated patients. The highest area under the ROC curve was observed in patients with pNET harbouring MEN1 mutations.

Conclusion and relevance: This study highlights the distinct plasma metabolic signatures of pNETs, including the critical role of FAO and elevated glutamate levels in metastasis, supporting the energy and biosynthetic needs of rapidly proliferating tumour cells. Mapping of these dysregulated metabolites may facilitate the identification of new therapeutic targets for pNETs management.

利用代谢组学方法鉴定胰腺神经内分泌肿瘤的代谢物生物标志物。
目的:代谢灵活性是癌症的一个重要标志,反映了与代谢物相关的异常肿瘤变化。胰腺神经内分泌肿瘤(pNETs)的代谢可塑性在很大程度上仍未被研究。值得注意的是,pNETs的异质性使其诊断、预后和治疗管理复杂化。在这里,我们比较了pNET患者和非癌症个体的血浆代谢组学特征,以了解代谢失调。设计和方法:采用LC-MS/MS和FIA-MS/MS (Biocrates AbsoluteIDQ p180试剂盒)分析76例pNETs患者和38例非癌个体的血浆代谢谱。统计分析包括单变量和多变量方法,并生成受试者工作特征(ROC)曲线,用于代谢组学特征识别。结果:与非癌个体相比,pNET患者表现出磷酸甘油酯代谢物水平升高和酰基肉碱水平降低,表明脂肪酸氧化(FAO)上调,这对pNET细胞的能量代谢和一碳代谢代谢物至关重要。转移性pNETs患者中观察到谷氨酸水平升高和脂质代谢物水平降低。与非MEN1突变患者相比,种系MEN1突变患者的氨基酸代谢物和FAO较低,与亮氨酸分解代谢和脂质代谢相关的代谢物增加。携带MEN1突变的pNET患者的ROC曲线下面积(AUC)最高。结论:本研究强调了pNETs独特的血浆代谢特征,包括FAO和谷氨酸水平升高在转移中的关键作用,支持快速增殖肿瘤细胞的能量和生物合成需求。这些失调代谢物的定位可能有助于确定pNETs管理的新治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
European Journal of Endocrinology
European Journal of Endocrinology 医学-内分泌学与代谢
CiteScore
9.80
自引率
3.40%
发文量
354
审稿时长
1 months
期刊介绍: European Journal of Endocrinology is the official journal of the European Society of Endocrinology. Its predecessor journal is Acta Endocrinologica. The journal publishes high-quality original clinical and translational research papers and reviews in paediatric and adult endocrinology, as well as clinical practice guidelines, position statements and debates. Case reports will only be considered if they represent exceptional insights or advances in clinical endocrinology. Topics covered include, but are not limited to, Adrenal and Steroid, Bone and Mineral Metabolism, Hormones and Cancer, Pituitary and Hypothalamus, Thyroid and Reproduction. In the field of Diabetes, Obesity and Metabolism we welcome manuscripts addressing endocrine mechanisms of disease and its complications, management of obesity/diabetes in the context of other endocrine conditions, or aspects of complex disease management. Reports may encompass natural history studies, mechanistic studies, or clinical trials. Equal consideration is given to all manuscripts in English from any country.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信