您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报(医学版) ›› 2016, Vol. 54 ›› Issue (7): 60-68.doi: 10.6040/j.issn.1671-7554.0.2016.013

• • 上一篇    下一篇

基于GC-TOF-MS的结直肠癌代谢组学差异分析

于斐,刘少壮,仲明惟,黄鑫,焦杰,胡三元,于文滨   

  1. 山东大学齐鲁医院普外科, 山东 济南 250012
  • 收稿日期:2016-01-06 出版日期:2016-07-10 发布日期:2016-07-10
  • 通讯作者: 于文滨. E-mail:wenbin_yu2003@aliyun.com E-mail:wenbin_yu2003@aliyun.com
  • 基金资助:
    泰山学者工程专项经费、山东省医学领军人才、山东省优秀中青年科学家科研奖励基金(BS2013YY031)

Metabolomics analysis of colorectal cancer based on GC-TOF-MS

YU Fei, LIU Shaozhuang, ZHONG Mingwei, HUANG Xin, JIAO Jie, HU Sanyuan, YU Wenbin   

  1. Department of Surgery, Qilu Hospital Affiliated to Shandong University, Jinan 250012, Shandong, China
  • Received:2016-01-06 Online:2016-07-10 Published:2016-07-10

摘要: 目的 探讨结直肠癌(CRC)患者癌组织、癌旁黏膜及正常黏膜的代谢差异。 方法 选取25例CRC患者,分别取癌组织、癌旁黏膜和正常黏膜各1份,采用气相色谱-飞行时间-质谱(GC-TOF-MS)分析平台对组织样本进行代谢组学检测,3种组织间相互比较并采用主成分分析和正交偏最小二乘判别分析对数据建模,分析差异代谢物并在KEGG数据库中映射,找出相关代谢通路。 结果 与正常黏膜相比,癌组织中有47种差异代谢物(P<0.05, q<0.05),其半乳糖代谢、磷酸戊糖途径、谷氨酸和谷氨酰胺代谢及谷氨酸、丙氨酸和天冬氨酸代谢明显改变(P<0.05);癌旁黏膜中有3种差异代谢物(P<0.05, q<0.05),其半乳糖代谢明显改变(P<0.05)。癌组织与癌旁黏膜相比,有34种差异代谢物(P<0.05, q<0.05),其半乳糖代谢、磷酸戊糖途径、谷氨酸和谷氨酰胺代谢及谷氨酸、丙氨酸和天冬氨酸代谢明显改变(P<0.05)。 结论 CRC癌组织中糖代谢和氨基酸代谢发生改变。

关键词: 代谢组学, 氨基酸代谢, 结直肠肿瘤, 糖代谢

Abstract: Objective To explore the metabolic differences of cancer tissues, adjacent mucosa and normal mucosa in patients with colorectal cancer(CRC). Methods A total of 25 CRC patients were selected and the 3 kinds of tissues were taken from each patient. Gas chromatography time-of-flight mass spectrometry(GC-TOF-MS)platform was used for metabolomics analysis. The tissues were compared among each other, and principal components analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)were used to analyze the data. Differential metabolites were mapped in the KEGG database to search for the related metabolic pathways. Results Compared with the normal mucosa, 47 metabolites were found different(P<0.05, q<0.05)in cancer tissues, and galactose metabolism, pentose phosphate pathway, glutamate and glutamine metabolism, glutamate, alanine and aspartate metabolism changed significantly(P<0.05). In the adjacent mucosa, 3 metabolites were found different(P<0.05, q<0.05), and galactose metabolism changed significantly(P<0.05). A total of 34 metabolites were found different(P<0.05, q<0.05)between the cancer tissues and the adjacent mucosa, and pentose phosphate pathway, glutamate and glutamine metabolism, glutamate, alanine and aspartate metabolism changed significantly(P<0.05). Conclusion The glucose metabolism and amino acid metabolism are changed in CRC tissues.

Key words: Metabolomics, Glucose metabolism, Colorectal neoplasms, Amino acid metabolism

中图分类号: 

  • R605
[1] Jemal A, Bray F, Center MM, et al. Global cancer statistics[J]. CA Cancer J Clin, 2011, 61(2): 69-90.
[2] 陈万青, 张思维, 曾红梅, 等. 中国 2010 年恶性肿瘤发病与死亡[J]. 中国肿瘤, 2014, 23(1): 1-10. CHEN Wanqing, ZHANG Siwei, ZENG Hongmei, et al. Report of cancer incidence and mortality in china, 2010[J]. China Cancer, 2014, 23(1): 1-10.
[3] 王宁,孙婷婷,郑荣寿,等.中国 2009 年结直肠癌发病和死亡资料分析[J].中国肿瘤, 2013, 22(7): 515-520. WANG Ning, SUN Tingting, ZHENG Rongshou, et al. An analysis of incidence and mortality of colorectal cancer in china, 2009[J]. China Cancer, 2013, 22(7): 515-520.
[4] Ni Y, Xie G, Jia W, et al. Metabonomics of human colorectal cancer: new approaches for early diagnosis and biomarker discovery[J]. J Proteome Res, 2014, 13(9): 3857-3870.
[5] Zhu J, Djukovic D, Deng L, et al. Colorectal cancer detection using targeted serum metabolic profiling[J]. J Proteome Res, 2014, 13(9): 4120-4130.
[6] Ma Y, Zhang P, Wang F, et al. An integrated proteomics and metabolomics approach for defining oncofetal biomarkers in the colorectal cancer[J]. Ann Surg, 2012, 255(4): 720-730.
[7] 马延磊, 刘伟杰, 彭佳远, 等. 基于气相色谱-质谱联用的结直肠癌代谢组模式特征性研究[J]. 中华胃肠外科杂志, 2009, 12(4): 386-390. MA Yanlei, LIU Weijie, PENG Jiayuan, et al. Study on specific metabonomic profiling of serum from colorectal cancer patients by gas chromatography-mass spectrometry[J]. Chin J Gastrointest Surg, 2009, 12(4): 386-390.
[8] Nishiumi S, Kobayashi T, Ikeda A, et al. A novel serum metabolomics-based diagnostic approach for colorectal cancer[J]. PLoS One, 2012, 7(7): e40459. doi:10.1371/journal.pone.0040459.
[9] Hung JS, Huang J, Lin YC, et al. C1GALT1 overexpression promotes the invasive behavior of colon cancer cells through modifying O-glycosylation of FGFR2[J]. Oncotarget, 2014, 5(8): 2096-2106.
[10] Williams MD, Zhang X, Belton AS, et al. HMGA1 drives metabolic reprogramming of intestinal epithelium during hyperproliferation, polyposis, and colorectal carcinogenesis[J]. J Proteome Res, 2015, 14(3): 1420-1431.
[11] Chan EC, Koh PK, Mal M, et al. Metabolic profiling of human colorectal cancer using high-resolution magic angle spinning nuclear magnetic resonance(HR-MAS NMR)spectroscopy and gas chromatography mass spectrometry(GC/MS)[J]. J Proteome Res, 2009, 8(1): 352-361.
[12] Mal M, Koh PK, Cheah PY, et al. Metabotyping of human colorectal cancer using two-dimensional gas chromatography mass spectrometry[J]. Anal Bioanal Chem, 2012, 403(2): 483-493.
[13] Qiu Y, Cai G, Zhou B, et al. A distinct metabolic signature of human colorectal cancer with prognostic potential[J]. Clin Cancer Res, 2014, 20(8): 2136-2146.
[14] Vizán P, Alcarraz-Vizán G, Díaz-Moralli S, et al. Modulation of pentose phosphate pathway during cell cycle progression in human colon adenocarcinoma cell Line HT29[J]. Int J Cancer, 2009, 124(12): 2789-2796.
[15] Shibuya N, Inoue K, Tanaka G, et al. Augmented pentose phosphate pathway plays critical roles in colorectal carcinomas[J]. Oncology, 2015, 88(5): 309-319.
[16] Huang F, Zhang Q, Ma H, et al. Expression of glutaminase is unregulated in colorectal cancer and of clinical significance[J]. Int J Clin Exp Pathol, 2014, 7(3): 1093-1100.
[17] Liu G, Zhu J, Yu M, et al. Glutamate dehydrogenase is a novel prognostic marker and predicts metastases in colorectal cancer patients[J]. J Transl Med, 2015, 13: 144.
[18] 张文静, 卿国良. 谷氨酰胺代谢与肿瘤[J]. 生命科学, 2013, 25(11): 1109-1114. ZHANG Wenjing, QING Guoliang. Glutamine metabolism and cancer[J]. Life of Science, 2013, 25(11): 1109-1114.
[19] Yang L, Moss T, Mangala LS, et al. Metabolic shifts toward glutamine regulate tumor growth, invasion and bioenergetics in ovarian cancer[J]. Mol Syst Biol, 2014, 10: 728. doi: 10.1002/msb.20134892.
[20] Ikeda A, Nishiumi S, Shinohara M, et al. Serum metabolomics as a novel diagnostic approach for gastrointestinal cancer[J]. Biomed Chromatogr, 2012, 26(5): 548-558.
[1] 吴雪燕,高英静,刘思言,王少莲. 以手足及面部麻木为首发表现的青少年孤立肾漏诊1例并文献复习[J]. 山东大学学报 (医学版), 2024, 62(3): 121-124.
[2] 浩妍,崔丽梅,陈颖,杨玉娟,宋西成. 代谢组学在气道炎症性疾病中的应用[J]. 山东大学学报 (医学版), 2024, 62(12): 117-124.
[3] 景凯,徐志伟,李乐平. 基于GEO数据库探究结直肠肿瘤相关基因及其功能[J]. 山东大学学报 (医学版), 2024, 62(1): 21-30.
[4] 王智璠,林小仙,阴佳璐,王东亮,王姝麒. 不同炖煮温度燕窝次生代谢化学成分组学[J]. 山东大学学报 (医学版), 2023, 61(4): 10-17.
[5] 黄珊,娄能俊,韩晓琳,梁中昊,华梦羽,庄向华,陈诗鸿. 高糖环境下Lipin1对神经元代谢组学的影响[J]. 山东大学学报 (医学版), 2023, 61(2): 1-8.
[6] 芦兴晨,强晔,刘昕宇,左丹,姜子晗,张玉超,刘元涛,马小莉. NR4A1对毒胡萝卜素诱导C2C12肌管细胞糖代谢功能障碍的影响[J]. 山东大学学报 (医学版), 2023, 61(11): 38-47.
[7] 苑宝文,王沛,黄蔚. 组蛋白去乙酰化酶SIRT1对胰腺癌代谢的调控作用[J]. 山东大学学报 (医学版), 2022, 60(3): 1-12.
[8] 李晗,曹学峰,张兴元,成雨,孔令群. 原发性乙状结肠鳞癌1例[J]. 山东大学学报 (医学版), 2021, 59(10): 122-124.
[9] 扈艳雯,王志媛,郁万江,赵蕙琛,韩合理,徐志鹏,马红,张玉超,刘元涛. 52例肥胖患者脂肪分布与代谢综合征及糖代谢指标的相关性[J]. 山东大学学报 (医学版), 2020, 1(8): 101-106.
[10] 孙凤娇,李艳,王雨心,张天然,吴虹,高希宝. 膳食结构与硒对大鼠糖代谢的作用[J]. 山东大学学报 (医学版), 2020, 58(2): 36-43.
[11] 章海容, 张小红, 王超群. 哺乳动物雷帕霉素靶蛋白通路调控ECA109细胞放疗敏感性的代谢组学[J]. 山东大学学报 (医学版), 2020, 58(1): 6-12.
[12] 王美建,侯新国,梁凯,陈丽. 山东省城市中老年人群血脂现状调查[J]. 山东大学学报(医学版), 2017, 55(5): 70-75.
[13] 程向登,梁爽,胡艳艳,乔玉,王凤雪,李桂梅. Prader-Willi综合征患儿下丘脑-垂体-靶腺轴功能及代谢的改变[J]. 山东大学学报(医学版), 2017, 55(3): 107-111.
[14] 刘童,张欣,王传新. IRX5 mRNA在结直肠癌诊断及预后中的价值[J]. 山东大学学报(医学版), 2016, 54(7): 69-74.
[15] 赵琰,郑亚冰,闫新峰,张虎,常晓天. 筛选类风湿关节炎中糖代谢关键基因的探讨[J]. 山东大学学报(医学版), 2016, 54(3): 30-35.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!