|本期目录/Table of Contents|

[1]黄鑫,闫申,阮宏莹.头颈鳞癌与中心碳代谢通路研究[J].天津医科大学学报,2022,28(04):390-397.
 HUANG Xin,YAN Shen,RUAN Hong-ying.Study on central carbon metabolism pathway in head and neck squamous cell carcinoma[J].Journal of Tianjin Medical University,2022,28(04):390-397.
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头颈鳞癌与中心碳代谢通路研究(PDF)
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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
28卷
期数:
2022年04期
页码:
390-397
栏目:
基础医学
出版日期:
2022-07-20

文章信息/Info

Title:
Study on central carbon metabolism pathway in head and neck squamous cell carcinoma
文章编号:
1006-8147(2022)04-0390-08
作者:
黄鑫1闫申2阮宏莹13
(1.天津医科大学一中心临床学院,天津 300192;2.天津医科大学口腔医学院,天津 300070;3. 中南大学湘雅医学院附属海口医院耳鼻咽喉头颈外科,海口570000)
Author(s):
HUANG Xin1YAN Shen2RUAN Hong-ying13
(1.First Central Clinical School,Tianjin Medical University,Tianjin 300192,China;2.College of Stomatology,Tianjin Medical University,Tianjin 300070,China;3. Department of Otolaryngology-Head and Neck Surgery,Haikou Affiliated Hospital of Central South University Xiangya School of Medicine,Haikou 570000,China)
关键词:
头颈鳞状细胞癌转录组学蛋白质组学代谢组学平行反应监测
Keywords:
head and neck squamous cell carcinoma transcriptomics proteomics metabolomics parallel reaction monitoring
分类号:
R762
DOI:
-
文献标志码:
A
摘要:
目的:探究头颈鳞癌代谢重编程机制。方法:通过对头颈鳞癌和癌旁组织进行真核有参转录组学、TMT标记定量蛋白质组学和非靶向代谢组学分析,找到差异表达基因、蛋白质和代谢物,进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)富集分析等生物信息学分析,两两组学联合分析预测参与头颈鳞癌代谢重编程的重要代谢通路。然后进行平行反应监测(PRM)验证通路重要蛋白,找到差异表达蛋白及代谢通路。结果:联合分析结果提示,肿瘤中心碳代谢和蛋白质消化吸收途径可能与肿瘤有关。PRM结果表明,表皮生长因子受体(EGFR)、乳酸脱氢酶A(LDHA)、磷酸甘油酸酯转位酶1(PGAM1)、己糖激酶3(HK3)和磷酸果糖激酶(PFKP)在肿瘤中表达升高并参与肿瘤中心碳代谢途径。结论:肿瘤中心碳代谢通路及相关蛋白EGFR、 PGAM1、 LDHA、 HK3、 PFKP在头颈鳞癌发生、发展中起关键作用。
Abstract:
Objective: To investigate the metabolic mechanisms of head and neck squamous cell carcinoma(HNSCC). Methods: Eukaryotic transcriptomics,TMT labeled quantitative proteomics,and untargeted metabolomics on head and neck squamous cell carcinoma and adjacent tissues were performed to identify differentially expressed genes,proteins,and metabolites. Gene ontology(GO) enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis,and other bioinformatics analyses were performed. Integration analyses were carried out to predict important pathways involved in metabolic reprogramming in HNSCC and perform parallel reaction monitoring(PRM) were used to identify differentially expressed proteins and metabolic pathways. Results: Integration analyses indicated central carbon metabolism in cancer and protein digestion and absorption pathway might be relevant to tumorigenesis. In addition,the results of PRM clarified significantly elevated levels of epidermal growth factor receptor(EGFR),phosphoglycerate mutase 1(PGAM1),lactate dehydrogenase A(LDHA),Hexokinase 3(HK3),and phosphofructokinase(PFKP),which were consistent with central carbon metabolism. Conclusion: Central carbon metabolism in cancer is the critical metabolomic pathway in which EGFR,PGAM1,LDHA,HK3,PFKP play essential roles in the development of HNSCC.

参考文献/References:

[1] HORTON J D,KNOCHELMANN H M,DAY T A,et al. Immune evasion by head and neck cancer: foundations for combination therapy [J]. Trends Cancer,2019,5(4):208-232.
[2] PETERSON A C,RUSSELL J D,BAILEY D J,et al. Parallel reaction monitoring for high resolution and high mass accuracy quantitative,targeted proteomics[J]. Mol Cell Proteomics,2012,11(11):1475-1488.
[3] HANAHAN D,WEINBERG R A. Hallmarks of cancer:the next generation[J]. Cell,2011,144(5):646-674.
[4] LEONE R D,POWELL J D. Metabolism of immune cells in cancer[J]. Nat Rev Cancer,2020,20(9):516-531.
[5] FENDT S M,FREZZA C,EREZ A. Targeting metabolic plasticity and flexibility dynamics for cancer therapy[J]. Cancer Discov,2020,10(12):1797-1807.
[6] LI Z Q,WANG L L,ZHOU J,et al. Integration of transcriptomics and metabolomics profiling reveals the metabolic pathways affected in dictamnine-induced hepatotoxicity in mice[J]. J Proteomics,2020,213:103603.
[7] VAN DER MIJN J C,FU L,KHANI F,et al. Combined metabolomics and genome-wide transcriptomics analyses show multiple HIF1α-induced changes in lipid metabolism in early stage clear cell renal cell carcinoma[J]. Transl Oncol,2020,13(2):177-185.
[8] CHEN Y,NI J,GAO Y,et al. Integrated proteomics and metabolomics reveals the comprehensive characterization of antitumor mechanism underlying Shikonin on colon cancer patient-derived xenograft model[J]. Sci Rep,2020,10(1):14092.
[9] RAFIQ S,YEKU O O,JACKSON H J,et al. Targeted delivery of a PD-1-blocking scFv by CAR-T cells enhances anti-tumor efficacy in vivo[J]. Nat Biotechnol,2018,36(9):847-856.
[10] DE HOON M J,IMOTO S,NOLAN J,et al. Open source clustering software[J]. Bioinformatics,2004,20(9):1453-1454.
[11] SALDANHA A J. Java Treeview--extensible visualization of microarray data[J]. Bioinformatics,2004,20(17):3246-3248.
[12] YU C S,CHEN Y C,LU C H,et al. Prediction of protein subcellular localization[J]. Proteins,2006,64(3):643-651.
[13] YU C S,LIN C J,HWANG J K. Predicting subcellular localization of proteins for Gram-negative bacteria by support vector machines based on n-peptide compositions[J]. Protein Sci,2004,13(5):1402-1406.
[14] BLUM M,CHANG H Y,CHUGURANSKY S,et al. The InterPro protein families and domains database:20 years on[J]. Nucleic Acids Res,2021,49(D1):D344- D354.
[15] G?觟TZ S,GARCíA-GóMEZ J M,TEROL J,et al. High-throughput functional annotation and data mining with the Blast2GO suite[J]. Nucleic Acids Res,2008,36(10):3420-3435.
[16] CHOW L Q M. Head and neck cancer[J]. N Engl J Med,2020,382(1):60-72.
[17] ROTH K G,MAMBETSARIEV I,KULKARNI P,et al. The mitochondrion as an emerging therapeutic target in cancer[J]. Trends Mol Med,2020,26(1):119-134.
[18] LU J R. The Warburg metabolism fuels tumor metastasis[J]. Cancer Metast Rev,2019,38(1-2):157-164.
[19] MAKINOSHIMA H,TAKITA M,MATSUMOTO S,et al. Epidermal growth factor receptor(egfr) signaling regulates global metabolic pathways in egfr-mutated lung adenocarcinoma[J]. J Biol Chem,2014,289(30):20813-20823.
[20] MAKINOSHIMA H,TAKITA M,SARUWATARI K,et al. Signaling through the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) axis is responsible for aerobic glycolysis mediated by glucose transporter in epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma[J]. J Biol Chem,2015,290(28):17495-17504.
[21] DYRSTAD S E,LOTSBERG M L,TAN T Z,et al. Blocking aerobic glycolysis by targeting pyruvate dehydrogenase kinase in combination with egfr tki and ionizing radiation increases therapeutic effect in non-small cell lung cancer cells[J]. Cancers(Basel),2021,13(5):941.
[22] ZHANGYUAN G,WANG F,ZHANG H,et al. VersicanV1 promotes proliferation and metastasis of hepatocellular carcinoma through the activation of EGFR-PI3K-AKT pathway[J]. Oncogene,2020,39(6):1213-1230.
[23] LEE J H,LIU R,LI J,et al. EGFR-phosphorylated platelet isoform of phosphofructokinase 1 promotes PI3K activation[J]. Mol Cell,2018,70(2):197-210.
[24] WANG Y,NIE H,LIAO Z,et al. Expression and clinical significance of lactate dehydrogenase a in colon adenocarcinoma[J]. Front Oncol,2021,11:700795.
[25] KHAN A,SIDDIQUI S,HUSAIN S A,et al. Phytocompounds targeting metabolic reprogramming in cancer:an assessment of role,mechanisms,pathways,and therapeutic relevance[J]. J Agricul FoodChem,2021,69(25):6897-6928.
[26] GUO Y,LIANG F,ZHAO F L,et al. Resibufogenin suppresses tumor growth and Warburg effect through regulating miR-143-3p/HK2 axis in breast cancer[J]. Mol Cell Biochemy,2020,466(1-2):103-115.
[27] LV Z T,QI L,HU X H,et al. Identification of a novel glycolysis-related gene signature correlates with the prognosis and therapeutic responses in patients with clear cell renal cell carcinoma[J]. Front Oncol,2021,11:18.
[28] KIM N H,CHA Y H,LEE J,et al. Snail reprograms glucose metabolism by repressing phosphofructokinase PFKP allowing cancer cell survival under metabolic stress[J]. Nat Commun,2017,8:12.
[29] ZHANG Y M,LIU J K,WONG T Y. The DNA excision repair system of the highly radioresistant bacterium Deinococcus radiodurans is facilitated by the pentose phosphate pathway[J]. Molr Microbiol,2003,48(5):1317-1323.
[30] CHEN Y,XU Q,JI D X,et al. Inhibition of pentose phosphate pathway suppresses acute myelogenous leukemia[J]. Tumor Biol,2016,37(5):6027-6034.
[31] UMAR S M,KASHYAP A,KAHOL S,et al. Prognostic and therapeutic relevance of phosphofructokinase platelet-type(PFKP) in breast cancer [J]. Exp Cell Res,2020,396(1):10.
[32] HITOSUGI T,ZHOU L,ARELLANO M,et al. Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth [J]. Can Cell,2012,22(5):585-600.
[33] PENG X C,GONG F M,CHEN Y,et al. Proteomics identification of PGAM1 as a potential therapeutic target for urothelial bladder cancer [J]. J Proteomics,2016,132:85-92.
[34] SUN Q,LI S Z,WANG Y N,et al. Phosphoglyceric acid mutase-1 contributes to oncogenic mTOR-mediated tumor growth and confers non-small cell lung cancer patients with poor prognosis[J]. Cell Death Differ,2018,25(6):1160-1173.

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备注/Memo

备注/Memo:
作者简介:黄鑫(1996-),硕士在读,研究方向:头颈鳞癌代谢编程;通信作者:阮宏莹,E-mail:hongyingruan@tmu.edu.cn。
更新日期/Last Update: 2022-07-20