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On-line Access: 2024-05-10

Received: 2023-08-14

Revision Accepted: 2023-10-08

Crosschecked: 2024-05-10

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Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Chong LAI

0000-0002-6581-9987

Qingrong SUN

0000-0002-1616-7978

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Article info.

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.

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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",
volume="25",
number="5",
pages="410-421",
year="2024",
publisher="Zhejiang University Press & Springer",
doi="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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%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2300579

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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
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SP - 410
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PB - Zhejiang University Press & Springer
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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.

腎上腺嗜鉻細胞瘤影響三條主要代謝通路:半胱氨酸-蛋氨酸代謝、嘧啶代謝和酪氨酸代謝通路

來翀1,楊慶玲2,張雨諾2,龔人傑3,王馬傑4,李健康5,來茂德6,孫慶榮6
1浙江大(dà)學醫學院附屬第一(yī)醫院泌尿外(wài)科,中(zhōng)國杭州市,310003
2中(zhōng)國藥科大(dà)學基礎醫學與臨床藥學學院,中(zhōng)國南(nán)京市,210009
3浙江大(dà)學醫學院附屬第一(yī)醫院檢驗醫學科,中(zhōng)國杭州市,310003
4甯波大(dà)學醫學院附屬甯波康甯醫院行爲神經科學實驗室,甯波市微循環與莨菪類藥研究所,中(zhōng)國甯波市,315201
5西北(běi)工(gōng)業大(dà)學醫學研究院幹細胞與再生(shēng)醫學西安重點實驗室,中(zhōng)國西安市,710072
6中(zhōng)國醫學科學院腫瘤病理智能分(fēn)類與精準治療研究單元,浙江省疾病蛋白(bái)質組學重點實驗室,浙江大(dà)學醫學院病理學系,中(zhōng)國杭州市,310058
摘要:嗜鉻細胞瘤和副神經節瘤(PPGL)的臨床症狀主要是兒茶酚胺和肽類激素循環水平的改變。目前,PPGL的臨床診斷主要依賴于放(fàng)射影像和兒茶酚胺水平的檢測。本研究使用超高效液相色譜-四級杆-飛行時間質譜分(fēn)析法鑒定和測量腎上腺嗜鉻細胞瘤患者手術前後血漿中(zhōng)的差異代謝物(wù);通過對比嗜鉻細胞瘤與正常腎上腺髓質組織的轉錄組數據,獲得差異表達的基因列表。通過對發現數據集和驗證數據集兩部分(fēn)代謝組學分(fēn)析,發現健康組和患者組之間存在111個差異代謝物(wù),其中(zhōng)53個代謝物(wù)在驗證數據集中(zhōng)得到驗證。基于差異代謝物(wù)和差異表達基因數據,研究發現半胱氨酸-蛋氨酸代謝、嘧啶代謝和酪氨酸代謝通路是嗜鉻細胞瘤的三個主要改變的代謝途徑。轉錄水平分(fēn)析顯示,嗜鉻細胞瘤中(zhōng)酪氨酸代謝和半胱氨酸-蛋氨酸代謝通路均出現下(xià)調,而嘧啶代謝途徑則無明顯差異。最後,本研究構建了以L-二氫乳清酸和香草乙二醇爲輸入的最優診斷模型,并希望将L-二氫乳清酸和香草乙二醇作爲潛在的臨床生(shēng)物(wù)标志(zhì)物(wù),用于輔助嗜鉻細胞瘤的診斷。

關鍵詞:嗜鉻細胞瘤和副神經節瘤(PPGL);代謝組學;基因組差異分(fēn)析;L-二氫乳清酸;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.

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