Changes and clinical significance of plasma free amino acid levels in the development of chronic hepatitis B to hepatocellular carcinoma

doi:10.11958/20231456

Abstract

Abstract:

Objective To investigate changes and clinical significance in plasma free amino acid levels during the progression from chronic hepatitis B (CHB) to liver cirrhosis (LC) and ultimately to hepatocellular carcinoma (HCC). Methods The plasma samples of 49 CHB patients, 43 CHB-related LC patients and 50 CHB-related HCC patients were analyzed using the Hitachi L-8900 amino acid analyzer. The differences in amino acid levels were compared between groups. Simultaneously, the MetaboAnalyst website was used to analyze the relevant amino acid metabolism pathways. Results A total of 16 amino acids with different expression levels were identified. During the development from CHB to HCC, plasma levels of cystine, phenylalanine and glycine gradually increased, while the ratio of branched chain amino acids/aromatic amino acids gradually decreased. Compared with the CHB and the LC groups, levels of taurine, methionine, tyrosine, ornithine, glutamate, isoleucine and tryptophan were significantly increased in the HCC group, while the level of arginine was significantly lower. Compared with the CHB group, levels of serine, alanine and proline were higher in the LC and the HCC groups, while the level of valine was also higher in the HCC group (all P<0.05). The metabolic pathway analysis of three groups showed significant changes in various metabolic pathways, including phenylalanine, tyrosine, tryptophan biosynthesis, phenylalanine metabolism, glycine, serine, threonine metabolism, valine, leucine, isoleucine biosynthesis, and taurine metabolism. In addition, by constructing a network diagram of amino acid enzyme gene interactions, a total of 79 metabolic enzyme genes related to amino acid expression were discovered. Conclusion Plasma levels of amino acids are of certain guiding significance for early warning and prognosis of HCC and can provide a theoretical basis and methodological basis for the diagnosis and treatment of HCC in the future.

Key words: hepatitis B, chronic, liver cirrhosis, liver neoplasms, amino acids

CLC Number:

R575.1，R575.2，R735.7

Figures/Tables 6

References 19

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组别	n	年龄/岁	ALT/（U/L）	AST/（U/L）	γ-GGT/（U/L）	A/G	TBA/（μmol/L）
对照组	50	54.38±11.38	19.11±5.65	16.39±6.67	26.28（19.43，32.42）	1.59±0.62	6.85±1.75
CHB组	49	53.04±9.72	42.59±26.08^a	45.09±22.23^a	28.66（4.72，80.68）	1.62±0.73	17.94±8.14
LC组	43	52.51±10.28	46.93±31.42^a	44.15±38.24^a	60.64（12.59，189.93）^b	1.81±0.37	37.36±40.57^ab
HCC组	50	64.92±23.27^abc	48.83±35.47^a	82.26±62.76^abc	135.22（92.05，195.06）^abc	1.38±0.32^bc	45.34±43.07^ab
F或χ²		7.547^＊＊	12.756^＊＊	24.485^＊＊	43.558^＊＊	4.821^＊＊	17.538^＊＊
组别		TBIL/（μmol/L）		DBIL/（μmol/L）	ALP/（U/L）	ALB/（g/L）	AFP/（μg/L）
对照组		15.85±3.71		1.50（1.00，2.04）	65.77±17.77	47.02±5.21	0.23（0.17，0.27）
CHB组		17.94±11.61		2.68（1.92，3.48）^a	72.50±18.71	45.83±2.98	2.94（1.53，6.43）^a
LC组		22.60±22.25		2.52（0.64，5.35）	90.89±54.33^a	35.93±9.29^ab	10.57（3.81，19.72）^ab
HCC组		45.34±43.82^abc		4.77（1.81，52.67）^abc	139.93±82.50^abc	29.80±6.77^abc	237.64（118.79，352.43）^abc
F或χ²		14.117^＊＊		31.594^＊＊	21.487^＊＊	82.448^＊＊	151.355^＊＊

组别	n	年龄/岁	ALT/（U/L）	AST/（U/L）	γ-GGT/（U/L）	A/G	TBA/（μmol/L）
对照组	50	54.38±11.38	19.11±5.65	16.39±6.67	26.28（19.43，32.42）	1.59±0.62	6.85±1.75
CHB组	49	53.04±9.72	42.59±26.08^a	45.09±22.23^a	28.66（4.72，80.68）	1.62±0.73	17.94±8.14
LC组	43	52.51±10.28	46.93±31.42^a	44.15±38.24^a	60.64（12.59，189.93）^b	1.81±0.37	37.36±40.57^ab
HCC组	50	64.92±23.27^abc	48.83±35.47^a	82.26±62.76^abc	135.22（92.05，195.06）^abc	1.38±0.32^bc	45.34±43.07^ab
F或χ²		7.547^＊＊	12.756^＊＊	24.485^＊＊	43.558^＊＊	4.821^＊＊	17.538^＊＊
组别		TBIL/（μmol/L）		DBIL/（μmol/L）	ALP/（U/L）	ALB/（g/L）	AFP/（μg/L）
对照组		15.85±3.71		1.50（1.00，2.04）	65.77±17.77	47.02±5.21	0.23（0.17，0.27）
CHB组		17.94±11.61		2.68（1.92，3.48）^a	72.50±18.71	45.83±2.98	2.94（1.53，6.43）^a
LC组		22.60±22.25		2.52（0.64，5.35）	90.89±54.33^a	35.93±9.29^ab	10.57（3.81，19.72）^ab
HCC组		45.34±43.82^abc		4.77（1.81，52.67）^abc	139.93±82.50^abc	29.80±6.77^abc	237.64（118.79，352.43）^abc
F或χ²		14.117^＊＊		31.594^＊＊	21.487^＊＊	82.448^＊＊	151.355^＊＊

组别	n		牛磺酸	精氨酸		苏氨酸		丝氨酸		丙氨酸		胱氨酸		缬氨酸		蛋氨酸
CHB组	49		116.34±21.04	101.19±28.66		297.58±44.64		131.87±17.82		345.31±49.51		39.18±5.58		207.29±26.89		62.50±28.97
LC组	43		117.14±20.12	102.56±17.14		340.78±46.96^a		165.57±30.75^a		397.91±67.42^a		48.82±14.24^a		224.42±51.65		63.22±11.20
HCC组	50		150.53±82.73^ab	75.89±41.78^ab		283.62±72.11^b		163.32±38.59^a		407.76±96.27^a		58.77±20.04^ab		247.62±110.60^a		85.95±13.36^ab
F或χ²			6.894^＊＊	11.054^＊＊		12.630^＊＊		18.468^＊＊		10.007^＊＊		22.219^＊＊		3.777^＊		22.173^＊＊
组别		酪氨酸			苯丙氨酸		鸟氨酸		赖氨酸		脯氨酸		谷氨酸		甘氨酸
CHB组		89.64±23.95			95.55±9.55		95.62±60.60		170.85±26.19		158.44±50.34		125.66±37.66		228.65±32.59
LC组		108.63±30.78			109.47±18.05^a		96.89±28.26		181.21±43.06		183.21±36.28^a		136.98±48.14		253.82±46.14^a
HCC组		136.12±76.94^ab			130.36±49.98^ab		159.06±153.76^ab		179.77±70.71		181.68±62.42^a		198.50±110.61^ab		282.87±82.73^ab
F或χ²		10.518^＊＊			15.038^＊＊		6.501^＊＊		0.586		3.488^＊		13.695^＊＊		10.649^＊＊
组别				异亮氨酸		亮氨酸		组氨酸		色氨酸			天冬氨酸		支链氨基酸/芳香族基酸
CHB组				84.29±10.38		137.72±16.19		89.15±9.70		13.41±8.50			19.07（14.36，22.95）		3.10±1.10
LC组				90.68±30.00		143.69±44.08		92.55±14.38		17.24±8.34			18.11（11.81，22.77）		1.78±0.33^a
HCC组				108.24±57.67^ab		159.04±87.89		85.20±28.43		23.59±20.91^ab			13.59（3.57，113.21）		1.44±0.65^ab
F或χ²				5.120^＊＊		1.755		1.659		6.546^＊＊			2.341		63.358^＊＊

组别	n		牛磺酸	精氨酸		苏氨酸		丝氨酸		丙氨酸		胱氨酸		缬氨酸		蛋氨酸
CHB组	49		116.34±21.04	101.19±28.66		297.58±44.64		131.87±17.82		345.31±49.51		39.18±5.58		207.29±26.89		62.50±28.97
LC组	43		117.14±20.12	102.56±17.14		340.78±46.96^a		165.57±30.75^a		397.91±67.42^a		48.82±14.24^a		224.42±51.65		63.22±11.20
HCC组	50		150.53±82.73^ab	75.89±41.78^ab		283.62±72.11^b		163.32±38.59^a		407.76±96.27^a		58.77±20.04^ab		247.62±110.60^a		85.95±13.36^ab
F或χ²			6.894^＊＊	11.054^＊＊		12.630^＊＊		18.468^＊＊		10.007^＊＊		22.219^＊＊		3.777^＊		22.173^＊＊
组别		酪氨酸			苯丙氨酸		鸟氨酸		赖氨酸		脯氨酸		谷氨酸		甘氨酸
CHB组		89.64±23.95			95.55±9.55		95.62±60.60		170.85±26.19		158.44±50.34		125.66±37.66		228.65±32.59
LC组		108.63±30.78			109.47±18.05^a		96.89±28.26		181.21±43.06		183.21±36.28^a		136.98±48.14		253.82±46.14^a
HCC组		136.12±76.94^ab			130.36±49.98^ab		159.06±153.76^ab		179.77±70.71		181.68±62.42^a		198.50±110.61^ab		282.87±82.73^ab
F或χ²		10.518^＊＊			15.038^＊＊		6.501^＊＊		0.586		3.488^＊		13.695^＊＊		10.649^＊＊
组别				异亮氨酸		亮氨酸		组氨酸		色氨酸			天冬氨酸		支链氨基酸/芳香族基酸
CHB组				84.29±10.38		137.72±16.19		89.15±9.70		13.41±8.50			19.07（14.36，22.95）		3.10±1.10
LC组				90.68±30.00		143.69±44.08		92.55±14.38		17.24±8.34			18.11（11.81，22.77）		1.78±0.33^a
HCC组				108.24±57.67^ab		159.04±87.89		85.20±28.43		23.59±20.91^ab			13.59（3.57，113.21）		1.44±0.65^ab
F或χ²				5.120^＊＊		1.755		1.659		6.546^＊＊			2.341		63.358^＊＊

代谢通路	通路总数	氨基酸数	P值	FDR
苯丙氨酸、酪氨酸和色氨酸生物合成	27	3	0.000 003	0.028 8
苯丙氨酸代谢	18	3	0.000 321	0.017 3
缬氨酸、亮氨酸和异亮氨酸生物合成	59	1	0.005 300	0.050 1
牛磺酸代谢	12	1	0.007 031	0.057 4
甘氨酸、丝氨酸和苏氨酸代谢	59	6	0.000 032	0.000 2