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On-line Access: 2023-11-01

Received: 2023-08-14

Revision Accepted: 2023-10-08

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Journal of Zhejiang University SCIENCE B

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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, Hangzhou, China; more

Corresponding email(s):  sunqingrong@zju.edu.cn

Key Words:  Pheochromocytoma and paraganglioma (PPGL); Metabolomics; Gene set variation analysis; l-Dihyroorotic 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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Abstract: 
Pheochromocytomas and paragangliomas (PPGLs) cause symptoms by altering the circulation level 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 metabolism and cysteine and methionine were downregulated in pheochromocytoma, whereas the pyrimidine pathway showed no significant difference. Finally, we developed an optimized diagnostic model of two metabolites, L-dihyrorotic 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.

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