Serum Aldo-Keto Reductase Family 1 Member B10 (AKR1B10) as a Potential Biomarker for Diagnosis of Hepatocellular Carcinoma

Figures & data

Table 1 The Baseline Characteristics of the Subjects Included in This Study

Variables	HCC (n = 109)	HC (n = 165)	BLD (n = 106)	OC (n = 141)	P value for HCC vs HC	P value for HCC vs BLD	P value for HCC vs OC
Sex, n (%)					< 0.001	< 0.001	< 0.001
F	16 (15)	121 (73)	51 (48)	82 (58)
M	93 (85)	44 (27)	55 (52)	59 (42)
Age, Median (Q1, Q3)	57 (50, 63)	33 (28, 40)	43.5 (35, 54.75)	60 (49, 66)	< 0.001	< 0.001	0.053
AKR1B10, Median (Q1, Q3)	361.05 (130.94, 617.51)	87.73 (17.32, 154.15)	0 (0, 96.43)	0 (0, 46.31)	< 0.001	< 0.001	< 0.001
AFP, Median (Q1, Q3)	51.45 (5.07, 786.4)	2.1 (1.5, 3.2)	2.8 (1.8, 3.9)	2.75 (2.2, 4.28)	< 0.001	< 0.001	< 0.001
ALB, Median (Q1, Q3)	43 (40, 46)	46 (44.25, 47)	45 (41.75, 48)	44 (41, 46)	< 0.001	< 0.001	0.321
ALP, Median (Q1, Q3)	86 (69, 114)	53 (47.25, 64)	78.5 (64.75, 96.5)	79 (62.5, 93)	< 0.001	0.035	0.001
ALT, Median (Q1, Q3)	28 (20, 45)	14 (11, 18)	21.5 (15, 33)	15 (11, 20)	< 0.001	0.001	< 0.001
AST, Median (Q1, Q3)	32 (24, 49)	17 (16, 20)	24 (19, 32)	19 (17, 22)	< 0.001	< 0.001	< 0.001
CA19-9, Median (Q1, Q3)	20.1 (9.45, 28.8)	5.6 (3.05, 12.4)	11.25 (8.3, 18.6)	13.6 (6.6, 28)	< 0.001	0.007	0.222
CEA, Median (Q1, Q3)	2.49 (1.82, 3.3)	1.39 (1.1, 1.8)	1.44 (0.98, 1.87)	2.66 (1.93, 4.89)	< 0.001	< 0.001	0.102
Dbil, Median (Q1, Q3)	5.6 (4.3, 7.6)	3.9 (3.1, 4.8)	4.9 (3.5, 6.45)	4 (3.1, 4.8)	< 0.001	0.015	< 0.001
GGT, Median (Q1, Q3)	46 (32, 99)	14 (12, 20)	23.5 (17, 37)	20 (15, 32)	< 0.001	< 0.001	< 0.001
LD, Median (Q1, Q3)	192 (173, 222)	163 (148, 179)	178 (154.5, 212.25)	181 (161.5, 200.5)	< 0.001	0.039	0.002
Tbil, Median (Q1, Q3)	14.4 (12, 19.5)	11.4 (8.8, 13.8)	14 (9.75, 18.5)	11.6 (8.8, 15.1)	< 0.001	0.225	< 0.001
TC, Median (Q1, Q3)	4.07 (3.53, 4.79)	4.39 (3.92, 4.95)	4.39 (3.84, 5.08)	4.4 (3.94, 5.32)	0.102	0.213	< 0.001
TG, Median (Q1, Q3)	1.05 (0.77, 1.61)	0.74 (0.57, 1.02)	0.86 (0.68, 1.3)	1.19 (0.92, 1.69)	< 0.001	0.107	0.041
TP, Median (Q1, Q3)	71 (66, 75)	73 (70, 75)	72 (69, 75)	70 (65, 73)	0.011	0.089	0.185

Abbreviations: HCC, hepatocellular carcinoma; HC, healthy controls; BLD, benign liver diseases; OC, other cancers; AKR1B10, aldo-keto reductase family 1 member B10; AFP, alpha-fetoprotein; ALB, albumin; ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; CA19-9, carbohydrate antigen 19–9; CEA, carcinoembryonic antigen; Dbil, direct bilirubin; GGT, gamma-glutamyl transpeptidase; LD, lactic dehydrogenase; Tbil, total bilirubin; TC, total cholesterol; TG, total triglycerides; TP, total protein.

Figure 1 Serum AKR1B10 levels in various groups.

Abbreviations: AKR1B10, aldo-keto reductase family 1 member B10; HCC, hepatocellular carcinoma; HC, healthy controls; BLD, benign liver diseases; OC, other cancers.

Table 2 Association Between AKR1B10 Expression and the Clinicopathological Parameters of HCC Patients

Parameters	No. of Patients	ARK1B10		P value
		Negative	Positive
Age				0.301
<60	69	19	50
≥60	40	13	27
Sex				0.477
Male	93	29	64
Female	16	3	13
HBV				0.227
Negative	11	1	10
Positive	98	31	67
Differentiation				0.866
Poor	15	4	11
Moderate	70	21	49
Well	13	3	10
Tumor size				0.736
<3 cm	30	8	22
≥3 cm	70	21	49

Abbreviations: AKR1B10, aldo-keto reductase family 1 member B10; HBV, hepatitis B virus.

Figure 2 Correlation of serum AKR1B10 with other laboratory indicators.

Abbreviations: AKR1B10, aldo-keto reductase family 1 member B10; ALT, alanine transaminase; TP, total protein; ALB, albumin; GGT, gamma-glutamyl transpeptidase; ALP, alkaline phosphatase; AST, aspartate transaminase; LD, lactic dehydrogenase; AFP, alpha-fetoprotein; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19–9; Tbil, total bilirubin; Dbil, direct bilirubin; TC, total cholesterol; TG, total triglycerides.

Table 3 Diagnostic Parameters of AKR1B10, AFP, CEA, and CA19-9 to Distinguish HCC Group from Control Groups

Group	Indicators	Cut-off Value	Sen	Spe	PPV	NPV
HCC vs HC	AKR1B10	215.45	0.71	0.96	0.92	0.83
	AFP	4.25	0.81	0.91	0.85	0.88
	CEA	1.62	0.83	0.68	0.64	0.86
	CA19-9	11.45	0.69	0.74	0.63	0.79
	AFP+AKR1B10	0.33	0.90	0.96	0.93	0.93
HCC vs BLD	AKR1B10	73.31	0.71	0.85	0.82	0.75
	AFP	7.95	0.96	0.68	0.72	0.95
	CEA	1.85	0.74	0.73	0.53	0.88
	CA19-9	14.10	0.70	0.62	0.42	0.84
	AFP+AKR1B10	0.31	0.85	0.86	0.88	0.83
HCC vs OC	AKR1B10	51.91	0.77	0.89	0.90	0.75
	AFP	7.30	0.96	0.69	0.67	0.96
	CEA	4.09	0.32	0.84	0.67	0.55
	CA19-9	9.00	0.40	0.80	0.65	0.59
	AFP+AKR1B10	0.58	0.86	0.94	0.96	0.82
HCC vs AC	AKR1B10	219.94	0.71	0.91	0.68	0.92
	AFP	7.45	0.69	0.97	0.87	0.90
	CEA	1.63	0.83	0.51	0.36	0.90
	CA19-9	11.55	0.69	0.63	0.39	0.85
	AFP+AKR1B10	0.12	0.89	0.91	0.77	0.96

Abbreviations: Sen, sensitivity; Spe, specificity; PPV, positive predictive value; NPV, negative predictive value; HCC, hepatocellular carcinoma; HC, healthy controls; BLD, benign liver diseases; OC, other cancers; AC, all controls; AKR1B10, aldo-keto reductase family 1 member B10; AFP, alpha-fetoprotein; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19–9.

Figure 3 Diagnostic performance of serum AKR1B10, AFP, CEA, and CA19-9 in HCC. (A–D) ROC curves of serum AKR1B10, AFP, CEA and CA19-9 differentiating HCC from HC, BLD, OC, and AC groups; (E–H) ROC curves of combining serum AKR1B10 with AFP differentiating HCC from HC, BLD, OC, and AC groups.

Abbreviations: HCC, hepatocellular carcinoma; HC, healthy controls; BLD, benign liver diseases; OC, other cancers; AC, all controls; AKR1B10, aldo-keto reductase family 1 member B10; AFP, alpha-fetoprotein; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19–9.

Table 4 Positive Rates of Serum AKR1B10, AFP, CEA, and CA19-9 in HCC Patients

Indicators	Positive Cases	Negative Cases	Total Case	Positive Rate
AKR1B10	77	32	109	70.60%
AFP	59	49	108	54.60%
CEA	10	95	105	9.50%
CA19-9	20	83	103	19.40%

Abbreviations: AKR1B10, aldo-keto reductase family 1 member B10; AFP, alpha-fetoprotein; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19–9.

Table 5 Diagnostic Parameters of Serum AKR1B10 to Distinguish AFP-Negative HCC Group from Control Groups

Group	Cut-off Value	Sen	Spe	PPV	NPV
HCC vs HC	218.88	0.71	0.96	0.83	0.92
HCC vs BLD	129.67	0.79	0.78	0.88	0.63
HCC vs OC	83.39	0.82	0.82	0.93	0.61
HCC vs AC	223.36	0.71	0.91	0.49	0.96

Abbreviations: Sen, sensitivity; Spe, specificity; PPV, positive predictive value; NPV, negative predictive value; HCC, hepatocellular carcinoma; HC, healthy controls; BLD, benign liver diseases; OC, other cancers; AC, all controls; AKR1B10, aldo-keto reductase family 1 member B10.

Figure 4 Diagnostic performance of serum AKR1B10 in AFP-negative HCC. (A–D) ROC curves of serum AKR1B10 differentiating AFP-negative HCC from HC, BLD, OC, and AC groups.

Abbreviations: HCC, hepatocellular carcinoma; HC, healthy controls; BLD, benign liver diseases; OC, other cancers; AC, all controls; AKR1B10, aldo-keto reductase family 1 member B10.

Figure 5 Changes in serum AKR1B10 levels before and after surgery. (A) Serum AKR1B10 levels in HCC patients who underwent resection at pre-surgery, 1–2 days after surgery, and 3–4 days after surgery; (B) Positive proportions of serum AKR1B10 in HCC patients who underwent resection at pre-surgery, 1–2 days after surgery, and 3–4 days after surgery.

Abbreviations: T0, pre-surgery; T1, 1–2 days after surgery; T2, 3–4 days after surgery; AKR1B10, aldo-keto reductase family 1 member B10.