Analysis of serum metabolomics characteristics of 63 acute leukemia patients by liquid chromatography-mass spectrometry

doi:10.3877/cma.j.issn.1674-0785.2023.08.002

Abstract

Abstract:

Objective

To investigate whether acute leukemia patients have unique serum metabolomics characteristics by using liquid chromatography-mass spectrometry (LC-MS), to search for potential markers related to acute leukemia, and to preliminarily explore the related metabolic pathways involved.

Methods

A metabolite analysis based on LC-MS was perform to analyze the small molecule metabolites in the serum of 63 acute leukemia patients and 59 healthy donors. Multivariate analysis and t-test were used to screen the differential metabolites, and the metabolic pathways related to differential metabolites were explored through the MetaboAnalyst 4.0 analysis platform.

Results

LC-MS-based metabolomics analysis can be used to distinguish acute leukemia patients from healthy donors. Based on VIP value and t-test, 29 different metabolites were screened, and metabolic abnormalities were found in acute leukemia patients compared with healthy donors, mainly involving linoleic acid metabolism and phenylalanine, tyrosine, tryptophan, and arginine biosynthesis pathways.

Conclusion

LC-MS-based metabolomics can identify unique endogenous differential metabolites in the serum of acute leukemia patients, and the screened differential metabolites have potential for the clinical diagnosis and prediction of the risk of acute leukemia.

Key words: Metabolomic, Leukemia, Liquid chromatography-mass spectrometry (LC-MS), Metabolism pathway

Lei Wang, Meng Li, Wenli Sun, Rui Liu, Hongchun Wang, Guangze Lu, Ying Zhao, Jinyan Guo, Hongxing Liu. Analysis of serum metabolomics characteristics of 63 acute leukemia patients by liquid chromatography-mass spectrometry[J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(08): 850-857.

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https://zhlcyszz.cma-cmc.com.cn/EN/Y2023/V17/I08/850

Figures/Tables 8

References 18

1	孙于谦,黄晓军. 我国血液肿瘤治疗待解决的问题及对策 [J]. 中华内科杂志, 2021, 60(10): 857-859.
2	Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms [J]. Blood, 2016, 127(20): 2375-2390.
3	田鹤, 税光厚. 基于质谱技术的代谢组学分析方法研究进展 [J]. 生物技术报, 2021, 37(1): 24-31.
4	Syed GM, Amna JS, Tahir S, et al. Serum metabonomics of acute leukemia using nuclear magnetic resonance spectroscopy [J]. Scientific Reports, 2016, 6(1): 1-9.
5	Caocci G, Deidda M, Noto A, et al. Metabolomic analysis of patients with chronic myeloid leukemia and cardiovascular adverse events after treatment with tyrosine kinase inhibitors [J]. J Clin Med, 2020, 9(4): 1180.
6	杨冰玉, 费琴雯, 李晓莉, 等. 慢性粒细胞白血病伊马替尼与尼洛替尼代谢组学差异性研究 [J]. 白血病.淋巴瘤, 2017, 26(4): 199-203.
7	Aurich MK, Paglia G, Rolfsson O, et al. Prediction of intracellular metabolic states from extracellular metabolomic data [J]. Metabolomics, 2015, 11(3): 603-619.
8	张炎, 江凡, 高成璐, 等. 基于液质联用技术的急性淋巴细胞白血病血清代谢组学分析 [J]. 中国医院药学杂志, 2018, 38(4): 379-382.
9	Wang D, Tan G, Wang H, et al. Identification of novel serum biomarker for the detection of acute myeloid leukemia based on liquid chromatography-mass spectrometry [J]. J Pharm Biomed Anal, 2019, 166: 357-363.
10	李歌, 李晓咪, 陆慧敏, 等. 液相色谱质谱法对66例胃癌患者血清代谢组学特征的分析 [J]. 中华消化杂志, 2019, 39(1): 12-18.
11	Richter ME, Neugebauer S, Engelmann F, et al. Biomarker candidates for the detection of an infectious etiology of febrile neutropenia [J]. Infection, 2016, 44(2): 175-186.
12	Percival ME, Lai C, Estey E, et al. Bone marrow evaluation for diagnosis and monitoring of acute myeloid leukemia [J]. Blood Rev, 2017, 31(4): 185-192.
13	Ackermans EC, Mulders R, Te Boekhorst B, et al. Phenylalanine requirements of enterally fed term and preterm neonates [J]. Am J Clin Nutr, 2015, 101(6): 1155-1162.
14	郑雯洁, 徐雅男, 周秦毅, 等. 女性甲状腺乳头状癌代谢组学特征及其与肿瘤大小、淋巴结转移的关系[J]. 中华耳鼻咽喉头颈外科杂志, 2016, 51(2): 105-111.
15	Menendez JA, Lupu R. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis [J]. Nat Rev Cancer, 2007, 7(10): 763-777.
16	Stockard B, Garrett T, Guingab-Cagmat J, et al. Distinct Metabolic features differentiating FLT3-ITD AML from FLT3-WT childhood Acute Myeloid Leukemia [J]. Sci Rep, 2018, 8(1): 5534.
17	Guo J, Huan T. Evaluation of significant features discovered from different data acquisition modes in mass spectrometry-based untargeted metabolomics [J]. Anal Chim Acta, 2020, 1137: 37-46.
18	Yang F, Li Q, Xiang J, et al. NMR-based plasma metabolomics of adult B-cell acute lymphoblastic leukemia [J]. Mol Omics, 2021, 17(1): 153-159.

序号	t_R（min）	m/z	代谢物^a	分子式	VIP值^b	FC^c	P值^d
1	8.47	495.3320	LysoPC（16∶0）	C24H50NO7P	8.74539	0.71354	1.54E-05
2	8.58	521.3478	LysoPC［18∶1（11Z）］	C26H52NO7P	8.01708	0.5366	6.95E-10
3	12.08	759.5770	PC［16：0/18∶1（11Z）］	C42H82NO8P	5.88195	0.6987	1.35E-13
4	4.34	204.1230	L-Acetylcarnitine	C9H17NO4	5.50741	1.804	1.53E-11
5	2.86	113.0591	Creatinine	C4H7N3O	5.43284	1.4838	2.42E-11
6	8.32	543.3322	LysoPC［20∶4（8Z，11Z，14Z，17Z）］	C28H50NO7P	3.98532	0.68762	1.72E-06
7	8.22	493.3167	LysoPC［16∶1（9Z）］	C24H48NO7P	3.55381	0.38808	0.0001843
8	8.34	519.3322	LysoPC［18∶2（9Z，12Z）］	C26H50NO7P	3.24422	0.86074	0.015538
9	11.27	732.5535	PC［16∶0/16∶1（9Z）］	C40H78NO8P	3.19649	0.41615	1.03E-11
10	13.15	787.6086	PC［18∶0/18∶1（11Z）］	C44H86NO8P	2.90336	0.68014	7.95E-09
11	11.40	781.5605	PC［16∶0/20∶4（5Z，8Z，11Z，14Z）］	C44H80NO8P	2.43033	0.88478	0.00060132
12	8.81	507.3687	LysoPC（P-18∶0）	C26H54NO6P	2.35881	0.7064	6.47E-06
13	1.69	316.2481	Decanoylcarnitine	C17H33NO4	2.27363	6.0072	1.44E-05
14	8.96	280.2401	Linoleic acid	C18H32O2	2.10248	1.4443	0.00031934
15	8.92	304.240	Arachidonic acid	C20H32O2	2.10248	0.7799	2.16E-05
16	1.89	288.2169	L-Octanoylcarnitine	C15H29NO4	2.08788	6.8975	0.00019087
17	5.77	131.0696	Creatine	C4H9N3O2	2.08484	0.73435	3.39E-06
18	6.36	176.1031	Citrulline	C6H13N3O3	1.8913	2.4962	1.48E-26
19	8.48	546.3550	LysoPC［20∶3（5Z，8Z，11Z）］	C28H52NO7P	1.68454	0.71646	7.72E-06
20	11.69	783.5767	PC［16∶0/20∶3（5Z，8Z，11Z）］	C44H82NO8P	1.65813	0.91869	0.024966
21	14.33	812.6767	SM［d18∶1/24∶1（15Z）］	C47H93N2O6P	1.50266	0.8588	0.043113
22	11.91	733.5621	PC（16∶0/16∶0）	C40H80NO8P	1.48544	0.71236	3.52E-07
23	8.31	567.3323	LysoPC［22∶6（4Z，7Z，10Z，13Z，16Z，19Z）］	C30H50NO7P	1.47621	0.70463	0.0012554
24	4.63	166.0863	L-Phenylalanine	C9H11NO2	1.25002	0.69409	1.24E-07
25	8.43	569.3480	LysoPC［22∶5（7Z，10Z，13Z，16Z，19Z）］	C30H52NO7P	1.24515	0.64503	9.16E-06
26	8.11	467.3011	LysoPC（14∶0）	C22H46NO7P	1.20763	0.57021	0.068231
27	2.69	246.1699	Valerylcarnitine	C12H23NO4	1.10094	1.9351	4.98E-08
28	2.29	260.1856	L-Hexanoylcarnitine	C13H25NO4	1.09453	3.3024	0.00058559
29	6.17	147.0765	L-Glutamine	C5H10N2O3	1.09403	1.1196	0.0019576

序号	t_R（min）	m/z	代谢物^a	分子式	VIP值^b	FC^c	P值^d
1	8.47	495.3320	LysoPC（16∶0）	C24H50NO7P	8.74539	0.71354	1.54E-05
2	8.58	521.3478	LysoPC［18∶1（11Z）］	C26H52NO7P	8.01708	0.5366	6.95E-10
3	12.08	759.5770	PC［16：0/18∶1（11Z）］	C42H82NO8P	5.88195	0.6987	1.35E-13
4	4.34	204.1230	L-Acetylcarnitine	C9H17NO4	5.50741	1.804	1.53E-11
5	2.86	113.0591	Creatinine	C4H7N3O	5.43284	1.4838	2.42E-11
6	8.32	543.3322	LysoPC［20∶4（8Z，11Z，14Z，17Z）］	C28H50NO7P	3.98532	0.68762	1.72E-06
7	8.22	493.3167	LysoPC［16∶1（9Z）］	C24H48NO7P	3.55381	0.38808	0.0001843
8	8.34	519.3322	LysoPC［18∶2（9Z，12Z）］	C26H50NO7P	3.24422	0.86074	0.015538
9	11.27	732.5535	PC［16∶0/16∶1（9Z）］	C40H78NO8P	3.19649	0.41615	1.03E-11
10	13.15	787.6086	PC［18∶0/18∶1（11Z）］	C44H86NO8P	2.90336	0.68014	7.95E-09
11	11.40	781.5605	PC［16∶0/20∶4（5Z，8Z，11Z，14Z）］	C44H80NO8P	2.43033	0.88478	0.00060132
12	8.81	507.3687	LysoPC（P-18∶0）	C26H54NO6P	2.35881	0.7064	6.47E-06
13	1.69	316.2481	Decanoylcarnitine	C17H33NO4	2.27363	6.0072	1.44E-05
14	8.96	280.2401	Linoleic acid	C18H32O2	2.10248	1.4443	0.00031934
15	8.92	304.240	Arachidonic acid	C20H32O2	2.10248	0.7799	2.16E-05
16	1.89	288.2169	L-Octanoylcarnitine	C15H29NO4	2.08788	6.8975	0.00019087
17	5.77	131.0696	Creatine	C4H9N3O2	2.08484	0.73435	3.39E-06
18	6.36	176.1031	Citrulline	C6H13N3O3	1.8913	2.4962	1.48E-26
19	8.48	546.3550	LysoPC［20∶3（5Z，8Z，11Z）］	C28H52NO7P	1.68454	0.71646	7.72E-06
20	11.69	783.5767	PC［16∶0/20∶3（5Z，8Z，11Z）］	C44H82NO8P	1.65813	0.91869	0.024966
21	14.33	812.6767	SM［d18∶1/24∶1（15Z）］	C47H93N2O6P	1.50266	0.8588	0.043113
22	11.91	733.5621	PC（16∶0/16∶0）	C40H80NO8P	1.48544	0.71236	3.52E-07
23	8.31	567.3323	LysoPC［22∶6（4Z，7Z，10Z，13Z，16Z，19Z）］	C30H50NO7P	1.47621	0.70463	0.0012554
24	4.63	166.0863	L-Phenylalanine	C9H11NO2	1.25002	0.69409	1.24E-07
25	8.43	569.3480	LysoPC［22∶5（7Z，10Z，13Z，16Z，19Z）］	C30H52NO7P	1.24515	0.64503	9.16E-06
26	8.11	467.3011	LysoPC（14∶0）	C22H46NO7P	1.20763	0.57021	0.068231
27	2.69	246.1699	Valerylcarnitine	C12H23NO4	1.10094	1.9351	4.98E-08
28	2.29	260.1856	L-Hexanoylcarnitine	C13H25NO4	1.09453	3.3024	0.00058559
29	6.17	147.0765	L-Glutamine	C5H10N2O3	1.09403	1.1196	0.0019576

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