Diagnostic performance of serum origin recognition complex subunit 1 protein for hepatitis B virus-related hepatocellular carcinoma

Table 1 The characteristics of study subjects, n (%)/mean ± SD

Group	Subgroup	Number	Male	Age (year)	ALT (U/L)	AST (U/L)	ORC1 (ng/L)	ESPL1 (ng/L)	AFP (ng/mL)
HBV-infected group	HBV-S-Int	20	17 (85.0)	44.35 ± 8.06	29.70 ± 14.03	33.45 ± 8.70	1660.65 (1428.60, 2218.60)	484.58 (300.22, 553.09)	3.04 (1.70, 8.19)
	HBV-NS-Int	47	33 (70.2)	51.14 ± 9.86	25.21 ± 13.64	30.17 ± 9.03	954.75 (681.19, 1435.25)	231.41 (189.15, 281.58)	2.5 (1.69, 3.23)
	CHB	162	109 (67.3)	42.45 ± 10.07	23.00 ± 10.66	29.31 ± 16.96	914.68 (642.23, 1319.14)	198.34 (151.29, 260.22)	2.39 (1.92, 315)
	HBV-LC	154	121 (78.6)	47.31 ± 9.67	31.94 ± 19.73	37.31 ± 20.40	918.30 (638.24, 1466.50)	276.14 (220.62, 327.27)	2.45 (1.82, 3.89)
	HBV-HCC	96	85 (88.5)	49.13 ± 9.44	50.5 ± 47.13	50.69 ± 41.41	1077.07 (727.03, 1675.67)	439.00 (261.25, 641.72)	10.55 (3.61, 263.81)
Non-HBV-infected control group	Non-HBV-HCC	29	19 (65.5)	59.34 ± 9.98	24.48 ± 12.85	34.69 ± 16.81	749.54 (660.24, 1150.33)	245.62 (212.75, 438.93)	60.22 (3.62, 2842.69)
	Healthy control	44	21 (47.7)	38.18 ± 13.33	-	-	731.51 (503.39, 1043.57)	128.89 (105.02, 150.82)	-

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ORC1: Origin recognition complex subunit 1; ESPL1: Extra spindle pole bodies-like 1; AFP: Alpha-fetoprotein; HBV-S-Int: Hepatitis B virus S gene integration; HBV-NS-Int: Hepatitis B virus non-S gene integration; CHB: Chronic hepatitis B; HBV-LC: Hepatitis B virus-related liver cirrhosis; HBV-HCC: Hepatitis B virus-related hepatocellular carcinoma.

Table 2 Variable descriptions and assignments for logistic regression analysis

Variable	Description	Assignment and notes
X1	Gender	Female = 0, male = 1
X2	Age	≤ 45 years = 0, > 45 years = 1
X3	History of anti-HBV therapy	No = 0, unknown = 1, yes = 2
X4	HBV DNA load	Log10-transformed
X5	HBeAg status	Negative = 0, positive = 1
X6	HBsAg level	Log10-transformed
X7	ALT level	Measured value (U/L)
X8	AST level	Measured value (U/L)
X9	AFP level	Measured value (ng/mL)
X10	HBV integration	No = 0, yes = 1
Y	Serum ORC1 level	≤ median = 0, > median = 1

HBV: Hepatitis B virus; HBeAg: Hepatitis B e antigen; HBsAg: Hepatitis B surface antigen; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; AFP: Alpha-fetoprotein; ORC1: Origin recognition complex subunit 1.

Table 3 Univariate and multivariate logistic regression analysis of factors associated with elevated serum origin recognition complex subunit 1 levels

Factor	Univariate analysis			Multivariate analysis
	B	OR (95%CI)	P value	B	Adjusted OR (95%CI)	P value
Gender	-0.198	0.821	0.725	-0.751	0.472	0.358
Age	-1.168	0.311	0.034	-0.371	0.690	0.598
History of anti-HBV therapy	0.134	1.143	0.820	0.028	1.029	0.972
HBV DNA load	0.453	1.573	0.124	0.789	2.201	0.066
HBeAg status	-0.693	0.500	0.579	-2.140	0.118	0.297
HBsAg level	0.166	1.181	0.563	0.169	1.184	0.622
ALT level	0.002	1.002	0.904	-0.021	0.979	0.523
AST level	0.013	1.013	0.636	0.001	1.001	0.982
AFP level	0.000	1.000	0.533	0.023	1.023	0.690
HBV integration	2.955	19.200	0.000	2.919	18.518	0.002

OR: Odds ratio; CI: Confidence interval; HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen; HBeAg: Hepatitis B e antigen; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; AFP: Alpha-fetoprotein.

Table 4 Receiver operating characteristic curve analysis of serum biomarkers in the diagnosis of hepatitis B virus-related hepatocellular carcinoma

Group	AUC	Youden’s index	Cut-off value	95%CI	Z value	P value
ORC1	0.587	0.204	967.814	0.520-0.653	2.599	0.012
ESPL1	0.776b	0.579	345.654	0.713-0.893	8.547	< 0.001
AFP	0.844b	0.566	400.000	0.794-0.984	13.498	< 0.001
ORC1 + ESPL1 + AFP	0.887a,b	0.686	0.152	0.784-0.891	17.541	< 0.001

^aP < 0.05 vs ESPL1.

^bP < 0.05 vs ORC1.

AUC: Area under the curve; CI: Confidence interval; ORC1: Origin recognition complex subunit 1; ESPL1: Extra spindle pole bodies-like 1; AFP: Alpha-fetoprotein.

Table 5 Diagnostic reliability analysis of serum biomarkers for hepatitis B virus-related hepatocellular carcinoma, (n/N, %)

Group	Sensitivity	Specificity	Accuracy	PPV	NPV
ORC1	65.56 (59/90, 0.551-0.750)	54.84 (170/310, 0.493-0.603)	57.25 (229/400, 0.523-0.621)	29.65 (59/199, 0.235-0.365)	84.58 (170/201, 0.792-0.889)
ESPL1	71.11 (64/90, 0.612-0.798)	86.77 (269/310, 0.827-0.901)	83.25 (333/400, 0.792-0.868)	60.95 (64/105, 0.514-0.697)	91.19 (269/295, 0.876-0.939)
AFP	21.11 (19/90, 0.138-0.309)	100.00 (310/310, 0.988-1.000)	82.25 (329/400, 0.782-0.858)	100.00 (19/19, 0.824-1.000)	81.36 (310/381, 0.773-0.849)
ORC1 + ESPL1 + AFP	84.44a,b (76/90, 0.756-0.909)	84.19c (261/310, 0.798-0.879)	84.25c (337/400, 0.803-0.876)	60.80 (76/125, 0.521-0.690)	94.91 (261/275, 0.917-0.971)

^aP < 0.05 vs ESPL1.

^bP < 0.05 vs AFP.

^cP < 0.05 vs ORC1.

PPV: Positive predictive value; NPV: Negative predictive value; ORC1: Origin recognition complex subunit 1; ESPL1: Extra spindle pole bodies-like 1; AFP: Alpha-fetoprotein.