JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

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

Author(s): Chong LAI, Qingling YANG, Yunuo ZHANG, Renjie GONG, Majie WANG, Jiankang LI, Maode LAI, Qingrong SUN
Affiliation(s): Department of Urology, the First Affiliated Hospital, Zhejiang University School of Medicine,Hangzhou310003,China; more
Corresponding email(s): sunqingrong@zju.edu.cn
Key Words: Pheochromocytoma and paraganglioma (PPGL); Metabolomics; Gene set variation analysis; L-Dihydroorotic acid; Vanylglycol

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Chong LAI, Qingling YANG, Yunuo ZHANG, Renjie GONG, Majie WANG, Jiankang LI, Maode LAI, Qingrong SUN. Adrenal pheochromocytoma impacts three main pathways: cysteine-methionine, pyrimidine, and tyrosine metabolism[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2300579

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author="Chong LAI, Qingling YANG, Yunuo ZHANG, Renjie GONG, Majie WANG, Jiankang LI, Maode LAI, Qingrong SUN",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2300579"
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%T Adrenal pheochromocytoma impacts three main pathways: cysteine-methionine, pyrimidine, and tyrosine metabolism
%A Chong LAI
%A Qingling YANG
%A Yunuo ZHANG
%A Renjie GONG
%A Majie WANG
%A Jiankang LI
%A Maode LAI
%A Qingrong SUN
%J Journal of Zhejiang University SCIENCE B
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doi="https://doi.org/10.1631/jzus.B2300579"

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A1 - Chong LAI
A1 - Qingling YANG
A1 - Yunuo ZHANG
A1 - Renjie GONG
A1 - Majie WANG
A1 - Jiankang LI
A1 - Maode LAI
A1 - Qingrong SUN
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PB - Zhejiang University Press & Springer
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doi="https://doi.org/10.1631/jzus.B2300579"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

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.

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

来翀¹，杨庆玲²，张雨诺²，龚人杰³，王马杰⁴，李健康⁵，来茂德⁶，孙庆荣⁶
¹浙江大学医学院附属第一医院泌尿外科，中国杭州市，310003
²中国药科大学基础医学与临床药学学院，中国南京市，210009
³浙江大学医学院附属第一医院检验医学科，中国杭州市，310003
⁴宁波大学医学院附属宁波康宁医院行为神经科学实验室，宁波市微循环与莨菪类药研究所，中国宁波市，315201
⁵西北工业大学医学研究院干细胞与再生医学西安重点实验室，中国西安市，710072
⁶中国医学科学院肿瘤病理智能分类与精准治疗研究单元，浙江省疾病蛋白质组学重点实验室，浙江大学医学院病理学系，中国杭州市，310058
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。

关键词组：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

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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

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