Adrenal pheochromocytoma impacts three main pathways: cysteine-methionine, pyrimidine, and tyrosine metabolism

Chong LAI; Qingling YANG; Yunuo ZHANG; Renjie GONG; Majie WANG; Jiankang LI; Maode LAI; Qingrong SUN

doi:10.1631/jzus.B2300579

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Adrenal pheochromocytoma impacts three main pathways: cysteine-methionine, pyrimidine, and tyrosine metabolism

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Research Article | Updated：2024-05-09

Adrenal pheochromocytoma impacts three main pathways: cysteine-methionine, pyrimidine, and tyrosine metabolism
Adrenal pheochromocytoma impacts three main pathways: cysteine-methionine, pyrimidine, and tyrosine metabolism
肾上腺嗜铬细胞瘤影响三条主要代谢通路：半胱氨酸-蛋氨酸代谢、嘧啶代谢和酪氨酸代谢通路
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 25, Issue 5, Pages: 410-421(2024)
Affiliations：

1.Department of Urology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
2.School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China
3.Department of Laboratory Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
4.Laboratory of Behavioral Neuroscience, Ningbo Kangning Hospital, Ningbo Institute of Microcirculation and Henbane, School of Medicine, Ningbo University, Ningbo 315201, China
5.Xi’an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi’an 710072, China
6.Department of Pathology, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310058, China
Funds：
DOI：10.1631/jzus.B2300579
CLC：
CSTR：
Published： 15 May 2024 ，

Published Online： 12 March 2024 ，

Received： 14 August 2023 ，

Revised： 08 October 2023 ，

来翀,杨庆玲,张雨诺等.肾上腺嗜铬细胞瘤影响三条主要代谢通路：半胱氨酸-蛋氨酸代谢、嘧啶代谢和酪氨酸代谢通路[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(05):410-421.

Chong LAI, Qingling YANG, Yunuo ZHANG, et al. Adrenal pheochromocytoma impacts three main pathways: cysteine-methionine, pyrimidine, and tyrosine metabolism. [J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) 25(5):410-421(2024)
来翀,杨庆玲,张雨诺等.肾上腺嗜铬细胞瘤影响三条主要代谢通路：半胱氨酸-蛋氨酸代谢、嘧啶代谢和酪氨酸代谢通路[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(05):410-421. DOI： 10.1631/jzus.B2300579.

Chong LAI, Qingling YANG, Yunuo ZHANG, et al. Adrenal pheochromocytoma impacts three main pathways: cysteine-methionine, pyrimidine, and tyrosine metabolism. [J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) 25(5):410-421(2024) DOI： 10.1631/jzus.B2300579.

摘要

嗜铬细胞瘤和副神经节瘤（PPGL）的临床症状主要是儿茶酚胺和肽类激素循环水平的改变。目前，PPGL的临床诊断主要依赖于放射影像和儿茶酚胺水平的检测。本研究使用超高效液相色谱-四级杆-飞行时间质谱分析法鉴定和测量肾上腺嗜铬细胞瘤患者手术前后血浆中的差异代谢物；通过对比嗜铬细胞瘤与正常肾上腺髓质组织的转录组数据，获得差异表达的基因列表。通过对发现数据集和验证数据集两部分代谢组学分析，发现健康组和患者组之间存在111个差异代谢物，其中53个代谢物在验证数据集中得到验证。基于差异代谢物和差异表达基因数据，研究发现半胱氨酸-蛋氨酸代谢、嘧啶代谢和酪氨酸代谢通路是嗜铬细胞瘤的三个主要改变的代谢途径。转录水平分析显示，嗜铬细胞瘤中酪氨酸代谢和半胱氨酸-蛋氨酸代谢通路均出现下调，而嘧啶代谢途径则无明显差异。最后，本研究构建了以L-二氢乳清酸和香草乙二醇为输入的最优诊断模型，并希望将L-二氢乳清酸和香草乙二醇作为潜在的临床生物标志物，用于辅助嗜铬细胞瘤的诊断。

Abstract

Pheochromocytomas and paragangliomas (PPGLs) cause symptoms by altering the circulation levels of catecholamines and peptide hormones. Currently

the diagnosis of PPGLs relies on diagnostic imaging and the detection of catecholamines. In this study

we used ultra-performance liquid chromatography (UPLC)/quadrupole time-of-flight mass spectrometry (Q-TOF MS) analysis to identify and measure the perioperative differential metabolites in the plasma of adrenal pheochromocytoma patients. We identified differentially expressed genes by comparing the transcriptomic data of pheochromocytoma with the normal adrenal medulla. Through conducting two steps of metabolomics analysis

we identified 111 differential metabolites between the healthy group and the patient group

among which 53 metabolites were validated. By integrating the information of differential metabolites and differentially expressed genes

we inferred that the cysteine-methionine

pyrimidine

and tyrosine metabolism pathways were the three main metabolic pathways altered by the neoplasm. The analysis of transcription levels revealed that the tyrosine and cysteine-methionine metabolism pathways were downregulated in pheochromocytoma

whereas the pyrimidine pathway showed no significant difference. Finally

we developed an optimized diagnostic model of two metabolites

L-dihydroorotic acid and vanylglycol. Our results for these metabolites suggest that they may serve as potential clinical biomarkers and can be used to supplement and improve the diagnosis of pheochromocytoma.

关键词

嗜铬细胞瘤和副神经节瘤（PPGL）代谢组学基因组差异分析L-二氢乳清酸香草乙二醇

Keywords

Pheochromocytoma and paraganglioma (PPGL)MetabolomicsGene set variation analysisL-Dihydroorotic acidVanylglycol

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