Full Text:   <682>

Summary:  <164>

Suppl. Mater.: 

CLC number: 

On-line Access: 2024-05-10

Received: 2023-08-14

Revision Accepted: 2023-10-08

Crosschecked: 2024-05-10

Cited: 0

Clicked: 916

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Chong LAI

0000-0002-6581-9987

Qingrong SUN

0000-0002-1616-7978

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2024 Vol.25 No.5 P.410-421

http://doi.org/10.1631/jzus.B2300579


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


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.

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: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

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[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.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE