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

作　　者：Chong LAI Qingling YANG Yunuo ZHANG Renjie GONG Majie WANG Jiankang LI Maode LAI Qingrong SUN 

机构地区：[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 Celland 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

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2024年第5期410-421,共12页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：supported by the National Natural Science Foundation of China(No.82072811).

摘　　要：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：Pheochromocytoma and paraganglioma(PPGL) Metabolomics Gene set variation analysis L-Dihydroorotic acid Vanylglycol 

分 类 号：R737.11[医药卫生—肿瘤]