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On-line Access: 2024-08-27
Received: 2023-10-17
Revision Accepted: 2024-05-08
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Adrenal pheochromocytoma impacts three main pathways: cysteine-methionine, pyrimidine, and tyrosine metabolism
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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, 2024, 25(5): 410-421.
@article{title="Adrenal pheochromocytoma impacts three main pathways: cysteine-methionine, pyrimidine, and tyrosine metabolism",
author="Chong LAI, Qingling YANG, Yunuo ZHANG, Renjie GONG, Majie WANG, Jiankang LI, Maode LAI, Qingrong SUN",
journal="Journal of Zhejiang University Science B",
volume="25",
number="5",
pages="410-421",
year="2024",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2300579"
}
%0 Journal Article
%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
%V 25
%N 5
%P 410-421
%@ 1673-1581
%D 2024
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2300579
TY - JOUR
T1 - Adrenal pheochromocytoma impacts three main pathways: cysteine-methionine, pyrimidine, and tyrosine metabolism
A1 - Chong LAI
A1 - Qingling YANG
A1 - Yunuo ZHANG
A1 - Renjie GONG
A1 - Majie WANG
A1 - Jiankang LI
A1 - Maode LAI
A1 - Qingrong SUN
J0 - Journal of Zhejiang University Science B
VL - 25
IS - 5
SP - 410
EP - 421
%@ 1673-1581
Y1 - 2024
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2300579
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.
[1]AygunN,UludagM,2020.Pheochromocytoma and paraganglioma: from epidemiology to clinical findings.Sisli Etfal Hastan Tip Bul,54(2):159-168.
[2]BaxterMA,HunterP,ThompsonGR,et al.,1992.Phaeochromocytomas as a cause of hypotension.Clin Endocrinol (Oxf),37(3):304-306.
[3]BenjaminiY,HochbergY,1995.Controlling the false discovery rate: a practical and powerful approach to multiple testing.J R Stat Soc Series B Methodol,57(1):289-300.
[4]ChenPC,WangCT,2023.Rat pheochromocytoma PC12 cells in culture. In: Borges R (Ed.),Chromaffin Cells: Methods and Protocols. Humana,New York, p.3-15.
[5]DwightT,KimE,NovosT,et al.,2019.Metabolomics in the diagnosis of pheochromocytoma and paraganglioma.Horm Metab Res,51(7):443-450.
[6]EisenhoferG,KopinIJ,GoldsteinDS,2004.Catecholamine metabolism: a contemporary view with implications for physiology and medicine.Pharmacol Rev,56(3):331-349.
[7]ErlicZ,BeuschleinF,2019.Metabolic alterations in patients with pheochromocytoma.Exp Clin Endocrinol Diabetes,127(2-3):129-136.
[8]FarrugiaFA,CharalampopoulosA,2019.Pheochromocytoma.Endocr Regul,53(3):191-212.
[9]FlussR,FaraggiD,ReiserB,2005.Estimation of the youden index and its associated cutoff point.Biom J,47(4):458-472.
[10]HamrinB,1962.Sustained hypotension and shock due to an adrenaline-secreting phaeochromocytoma.Lancet,280(7247):123-124.
[11]HänzelmannS,CasteloR,GuinneyJ,2013.GSVA: gene set variation analysis for microarray and RNA-Seq data.BMC Bioinformatics,14:7.
[12]HuangYY,XuKL,LiuJY,et al.,2022.Promotion of adrenal pheochromocytoma (PC-12) cell proliferation and outgrowth using Schwann cell-laden gelatin methacrylate substrate.Gels,8(2):84.
[13]JiaSM,LiCB,LeiZQ,et al.,2021.Determinants of anxiety and depression among pheochromocytoma patients: a case-control study.Medicine (Baltimore),100(3):e24335.
[14]JochmanovaI,PacakK,2016.Pheochromocytoma: the first metabolic endocrine cancer.Clin Cancer Res,22(20):5001-5011.
[15]LeeS,NakamuraE,YangHF,et al.,2005.Neuronal apoptosis linked to EglN3 prolyl hydroxylase and familial pheochromocytoma genes: developmental culling and cancer.Cancer Cell,8(2):155-167.
[16]López-JiménezE,Gómez-LópezG,Leandro-GarciaLJ,et al.,2010.Research resource: transcriptional profiling reveals different pseudohypoxic signatures in SDHB and VHL-related pheochromocytomas.Mol Endocrinol,24(12):2382-2391.
[17]NaranjoJ,DoddS,MartinYN,2017.Perioperative management of pheochromocytoma.J Cardiothorac Vasc Anesth,31(4):1427-1439.
[18]PrejbiszA,LendersJWM,EisenhoferG,et al.,2011.Cardiovascular manifestations of phaeochromocytoma.J Hypertens,29(11):2049-2060.
[19]RehmanT,ShabbirMA,Inam-Ur-RaheemM,et al.,2020.Cysteine and homocysteine as biomarker of various diseases.Food Sci Nutr,8(9):4696-4707.
[20]RemachaL,Comino-MéndezI,RichterS,et al.,2017.Targeted exome sequencing of Krebs cycle genes reveals candidate cancer-predisposing mutations in pheochromocytomas and paragangliomas.Clin Cancer Res,23(20):6315-6324.
[21]StarkmanMN,CameronOG,NesseRM,et al.,1990.Peripheral catecholamine levels and the symptoms of anxiety: studies in patients with and without pheochromocytoma.Psychosom Med,52(2):129-142.
[22]UedaT,OkaN,MatsumotoA,et al.,2005.Pheochromocytoma presenting as recurrent hypotension and syncope.Intern Med,44(3):222-227.
[23]WuHY,GaoTJ,CaoYW,et al.,2021.Case report: pheochromocytoma in a 59-year-old woman presenting with hypotension.Front Cardiovasc Med,8:648725.
[24]WuTZ,HuEQ,XuSB,et al.,2021.ClusterProfiler 4.0: a universal enrichment tool for interpreting omics data.Innovation,2(3):100141.
[25]ZhaoHY,ZhaoYZ,JiaYM,et al.,2021.Pheochromocytoma with abdominal aortic aneurysm presenting as recurrent dyspnea, hemoptysis, and hypotension: a case report.World J Clin Cases,9(18):4754-4759.
[26]ZhouY,TaoL,ZhouX,et al.,2021.DHODH and cancer: promising prospects to be explored.Cancer Metab,9(1):22.
[27]ZuberSM,KantorovichV,PacakK,2011.Hypertension in pheochromocytoma: characteristics and treatment.Endocrinol Metab Clin North Am,40(2):295-311.
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