肝细胞癌病人血清微量元素和氨基酸变化的观察研究

doi:10.16139/j.1007-9610.2025.02.09

摘要/Abstract

摘要：

目的：探讨肝细胞癌（HCC）病人血清微量元素及氨基酸谱的变化特点，为临床诊治提供参考依据。方法：选取本院2024年1月至2024年4月期间肝胆外科手术治疗的HCC病人104例作为研究组，另选取同期139例胆道良性疾病病人作为对照组。采用火焰原子吸收光谱法检测两组血清中铜、锌、钙、镁、铁和铅6种微量元素含量，用液相色谱串联质谱法检测21种氨基酸水平。结果：与对照组相比，HCC组血清中铜水平明显升高（P<0.05），而锌、铁水平明显降低（P<0.05）。氨基酸谱分析发现，与对照组相比，HCC组酪氨酸、甲硫氨酸及苯丙氨酸水平升高（P<0.05），而缬氨酸、亮氨酸、异亮氨酸、谷氨酰胺及精氨酸水平降低（P<0.05）。对组间有统计学差异的微量元素和氨基酸进一步分析两者间相关性，铜与缬氨酸、亮氨酸之间存在负相关（P<0.05）；而锌、铁与缬氨酸、亮氨酸及异亮氨酸之间均存在显著正相关（P<0.01）。结论：HCC病人普遍存在微量元素失衡和氨基酸代谢改变现象，且二者可能存在一定的内在联系。

关键词: 肝细胞癌, 微量元素, 氨基酸

Abstract:

Objective To explore the changes in trace elements and amino acid profiles in serum of patients with hepatocellular carcinoma(HCC) providing a reference for clinical diagnosis and treatment.Methods A total of 104 patients with HCC who underwent surgical treatment in the Department of Hepatobiliary Surgery of our hospital from January 2024 to April 2024 were selected as the study group, and 139 patients with benign biliary diseases during the same period were selected as the control group. Atomic absorption spectrometry was used to detect the levels of six trace elements (copper, zinc, calcium, magnesium, iron, and lead) in the serum of both groups, and liquid chromatography-tandem mass spectrometry was used to measure the concentrations of 21 amino acids.Results Compared with the control group, the serum copper level in the HCC group was significantly increased (P<0.05), while the levels of zinc and iron were significantly decreased (P<0.05). Amino acid profile analysis revealed that, compared with the control group, the concentrations of tyrosine, methionine, and phenylalanine in the HCC group were increased (P<0.05), while the concentrations of valine, leucine, isoleucine, glutamine, and arginine were decreased (P<0.05). Further analysis of the correlation between trace elements and amino acids with statistical differences between the groups showed that copper was negatively correlated with valine and leucine (P<0.05), while zinc and iron were positively correlated with valine, leucine, and isoleucine (P<0.01).Conclusions Imbalances in trace elements and amino acid metabolism changes are common in patients with HCC, and there may be an intrinsic connection between the two.

Key words: Hepatocellular carcinoma(HCC), Trace element, Amino acid

中图分类号:

罗茜, 蒋咏梅, 马迪, 陆秋涯, 顾晓寒. 肝细胞癌病人血清微量元素和氨基酸变化的观察研究[J]. 外科理论与实践, 2025, 30(2): 146-150.

LUO Xi, JIANG Yongmei, MA Di, LU Qiuya, GU Xiaohan. Observation on changes of trace elements and amino acids in serum of patients with hepatocellular carcinoma[J]. Journal of Surgery Concepts & Practice, 2025, 30(2): 146-150.

图/表 3

表1

表2

表3

参考文献 20

[1]	BRAY F, LAVERSANNE M, SUNG H, et al. Global cancer statistics 2022:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3):229-263.
[2]	YANG X, TANG Z, LI J, et al. Esophagus cancer and essential trace elements[J]. Front Public Health,2022, 10:1038153
[3]	ISHIKAWA T. Branched-chain amino acids to tyrosine ratio value as a potential prognostic factor for hepatocellular carcinoma[J]. World J Gastroenterol, 2012, 18(17):2005-2008.
[4]	赵玉萍, 韩秀青, 薛书保, 等. 原发性肝癌患者血中微量元素与氨基酸浓度的变化分析[J]. 临床肝胆病杂志, 2015, 31(6):915-917.
	ZHAO Y P, HAN X Q, XUE S B, et al. Clinical analysis of blood amino acids and trace elements in patients with hepatocellular carcinoma[J]. J Clin Hepatol, 2015, 31(6):915-917.
[5]	温晓静. 血浆氨基酸变化对肝癌患者的影响[J]. 临床合理用药, 2014, 7(13):126-127.
	WEN X J. Effects of plasma amino acid changes on patients with liver cancer[J]. Chin J Clin Ration Drug Use, 2014, 7(13):126-127.
[6]	MOSSMANN D, MÜLLER C, PARK S, et al. Arginine reprograms metabolism in liver cancer via RBM39[J]. Cell, 2023, 186(23):5068-5083.e23.
[7]	ZHU J, THOMPSON C B. Metabolic regulation of cell growth and proliferation[J]. Nat Rev Mol Cell Biol, 2019, 20(7):436-450.
[8]	裴亚萍, 杨艳莉, 李娜, 等. 谷氨酰胺代谢在肿瘤治疗中的研究进展[J]. 江苏医药, 2021, 47(11):1174-1178.
	PEI Y P, YANG Y L, LI N, et al. Research progress of glutamine metabolism in tumor treatment[J]. Jiangsu Med J, 2021, 47(11):1174-1178.
[9]	徐仁应, 万燕萍, 沈婉蓉, 等. 谷氨酰胺对人肝癌细胞系SMMC-7721增殖影响的体外研究[J]. 胃肠病学, 2005, 10(3):148-152.
	XU R Y, WAN Y P, SHEN W R, et al. Effects of glutamine on proliferation of human hepatoma cell line SMMC-7221 in vitro[J]. Chin J Gastroenterol, 2005, 10(3):148-152.
[10]	王映翘, 杨密, 王茵, 等. 铜及铜相关蛋白在肿瘤中的研究进展[J]. 肿瘤代谢与营养电子杂志, 2022, 9(2):265-270.
	WANG Y Q, YANG M, WANG Y, et al. Research progress of copper and copper-related proteins in tumors[J]. Electron J Metab Nutr Cancer, 2022, 9(2):265-270.
[11]	陈蕾洁, 刘德良, 谭玉勇. 铜死亡在肝癌中的研究进展[J]. 中南大学学报(医学版), 2023, 48(9):1368-1376.
	CHEN L J, LIU D L, TAN Y Y. Research progress in cuproptosis in liver cancer[J]. J Cent S Univ(Med Sci), 2023, 48(9):1368-1376.
[12]	TAWARI P E, WANG Z, NAJLAH M, et al. The cytotoxic mechanisms of disulfiram and copper(ii) in cancer cells[J]. Toxicol Res (Camb), 2015, 4(6):1439-1442.
[13]	LI Y, WANG L H, ZHANG H T, et al. Disulfiram combined with copper inhibits metastasis and epithelial-mesenchymal transition in hepatocellular carcinoma through the NF-κB and TGF-β pathways[J]. J Cell Mol Med, 2018, 22(1):439-451. doi: 10.1111/jcmm.13334 pmid: 29148232
[14]	HIMOTO T, MASAKI T. Current trends on the involvement of zinc, copper, and selenium in the process of hepatocarcinogenesis[J]. Nutrients, 2024, 16(4):472.
[15]	SHIGEFUKU R, IWASA M, KATAYAMA K, et al. Hypozincemia is associated with human hepatocarcinogene-sis in hepatitis C virus-related liver cirrhosis[J]. Hepatol Res, 2019, 49(10):1127-1135.
[16]	OZEKI I, NAKAJIMAT, SUII H, et al. Predictors of hepatocellular carcinoma after hepatitis C virus eradication following direct-acting antiviral treatment: relationship with serum zinc[J]. J Clin Biochem Nutr, 2020, 66(3):245-252. doi: 10.3164/jcbn.19-98 pmid: 32523252
[17]	FANG A P, CHEN P Y, WANG X Y, et al. Serum copper and zinc levels at diagnosis and hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort[J]. Int J Cancer, 2019, 144(11):2823-2832.
[18]	YANG D, TIAN T, LI X, et al. ZNT1 and Zn 2+ control TLR4 and PD-L1 endocytosis in macrophages to improve chemotherapy efficacy against liver tumor[J]. Hepatology, 2024, 80(2):312-329.
[19]	翦耀文, 熊文婧, 刘也, 等. 血清微量元素水平与肝癌相关性的Meta分析[J]. 中南医学科学杂志, 2017, 45(1):42-47.
	JIAN Y W, XIONG W J, LIU Y, et al. Meta-analysis of the correlation between trace element levels and liver cancer[J]. Med Sci J Cent S China, 2017, 45(1):42-47.
[20]	CHEN L, MIN J, WANG F. Copper homeostasis and cuproptosis in health and disease[J]. Signal Transduct Target Ther, 2022, 7(1):378.

Trace elements	Control Group (n=139)	HCC Group (n=104)	t value	P value
Cu	15.2 ± 2.5	17.1 ± 3.7	4.59	<0.01
Zn	92.1 ± 13.1	87.8 ± 11.5	-2.71	<0.01
Ca	1.4 ± 0.1	1.4 ± 0.1	0.00	0.92
Mg	1.5 ± 0.1	1.5 ± 0.1	-0.64	0.52
Fe	8.1 ± 0.9	7.7 ± 1.1	-2.48	<0.05
Pb	16.8 ± 16.2	23.3 ± 62.3	1.04	0.24

Amino acid	Control group (n=139)	HCC group (n=104)	t value	P value
Glut	77.2 ± 35.5	84.8 ± 40.5	1.52	0.12
Asp	6.1 ± 1.7	6.5 ± 2.0	1.37	0.16
Asn	46.3 ± 7.8	47.1 ± 10.4	0.72	0.46
Ser	132.1 ± 28.9	134.7 ± 34.7	0.63	0.52
Lys	194.4 ± 35.0	182.3 ± 34.5	-2.69	0.08
Trp	50.8 ± 9.3	52.4 ± 13.3	0.98	0.30
Phe	63.2 ± 9.6	70.3 ± 13.1	4.68	<0.01
Met	24.8 ± 4.7	29.4 ± 8.2	5.10	<0.01
Thr	138.3 ± 36.1	144.6 ± 39.9	1.27	0.20
Leu	134.3 ± 26.2	115.2 ± 28.2	-5.39	<0.01
Ile	81.1 ± 19.1	72.6 ± 16.1	-3.78	<0.01
Val	264.2 ± 49.8	245.6 ± 54.0	-2.74	<0.05
Arg	63.4 ± 17.2	53.9 ± 18.1	-4.16	<0.01
Tyr	64.2 ± 12.3	79.0 ± 23.1	5.94	<0.01
His	86.8 ± 11.9	84.0 ± 15.0	-1.50	0.12
Orn	111.1 ± 35.3	113.1 ± 30.4	0.49	0.63
Ala	409.0 ± 96.1	396.0 ± 107.4	-0.98	0.32
Pro	170.5 ± 52.7	178.6 ± 71.2	0.98	0.31
Cit	32.2 ± 9.5	34.8 ± 14.7	1.54	0.10
Gly	229.3 ± 58.8	240.9 ± 64.9	1.43	0.15
Gln	733.8 ± 130.8	640.7 ± 167.8	-4.69	<0.01
BCAA/AAA	3.0 ± 0.5	1.8 ± 0.8	-3.86	<0.05

Correlation coefficient	Cu	Zn	Fe
Val	-0.146*	0.271^**	0.395^**
Met	-0.013	0.102	0.104
Ile	-0.064	0.180^**	0.252^**
Leu	-0.177^**	0.264^**	0.416^**
Tyr	0.016	0.121	0.173
Phe	0.026	0.122	0.105
Arg	-0.099	0.029	0.102
Gln	-0.122	-0.06	0.072