Construction and evaluation of a liver cancer risk prediction model based on machine learning

Table 1 Discrepancy analysis of patient study metrics between the training and validation cohorts

Variables	Total (n = 550)	Group		Z/χ2	P value
		Training set (n = 385)	Validation set (n = 165)
Age	53 (47, 59)	53 (47, 59)	53 (48, 58)	Z = -0.42	0.68
WBC (109/L)	4.09 (2.98, 5.70)	4.06 (2.97, 5.65)	4.21 (3.00, 5.76)	Z = -0.71	0.48
RBC (1012/L)	4.43 (3.83, 4.94)	4.46 (3.84, 4.96)	4.36 (3.83, 4.91)	Z = -0.43	0.67
HB (g/L)	141.00 (121.00, 156.00)	142.00 (121.00, 157.00)	137.00 (121.00, 155.00)	Z = -1.00	0.32
PLT (109/L)	88.00 (55.00, 138.00)	85.00 (55.00, 136.00)	92.00 (56.00, 142.00)	Z = -0.88	0.38
AFP (ng/mL)	7.42 (2.96, 110.14)	7.44 (2.95, 88.46)	7.27 (3.07, 167.59)	Z = -0.21	0.84
PIVKA-II (mAU/mL)	32.55 (20.48, 1555.89)	33.85 (20.89, 1839.88)	28.64 (19.52, 1157.19)	Z = -0.85	0.39
CEA (ng/mL)	2.22 (1.42, 3.40)	2.21 (1.35, 3.36)	2.35 (1.54, 3.44)	Z = -1.28	0.20
CA199 (ng/mL)	19.70 (10.43, 38.10)	19.75 (10.60, 38.92)	18.60 (9.37, 34.30)	Z = -0.88	0.38
CA125 (ng/mL)	25.41 (13.18, 123.00)	23.91 (12.77, 103.25)	27.90 (14.70, 148.90)	Z = -1.24	0.22
Sex, n (%)				χ² = 0.91	0.34
Male	406 (74.22)	288 (75.39)	118 (71.52)
Female	141 (25.78)	94 (24.61)	47 (28.48)

WBC: White blood cell; RBC: Red blood cell; HB: Hemoglobin level; PLT: Platelet; AFP: Alpha-fetoprotein; PIVKA-II: Protein induced by vitamin K absence or antagonist II; CEA: Carcinoembryonic antigen; CA: Carbohydrate antigen.

Table 2 Univariate analysis of study parameters in the hepatocellular carcinoma and cirrhosis groups, n (%)

Variables	Total (n = 385)	Group		Z/χ2	P value
		Cirrhosis (n = 195)	HCC (n = 190)
Age	53.00 (47.00, 59.00)	51.00 (44.00, 56.00)	55.00 (49.00, 60.00)	Z = -4.66	< 0.001
WBC (109/L)	4.06 (2.97, 5.65)	3.50 (2.52, 4.54)	4.65 (3.69, 6.40)	Z = -6.87	< 0.001
RBC (1012/L)	4.46 (3.84, 4.96)	4.13 (3.54, 4.79)	4.70 (4.11, 5.07)	Z = -5.18	< 0.001
HB (g/L)	142.00 (121.00, 157.00)	134.00 (113.00, 151.75)	149.00 (129.75, 160.00)	Z = -4.76	< 0.001
PLT (109/L)	85.00 (55.00, 136.00)	64.50 (48.25, 100.00)	122.00 (70.50, 168.25)	Z = -7.95	< 0.001
AFP (ng/mL)	7.44 (2.95, 88.46)	3.79 (2.34, 9.32)	49.16 (5.84, 1220.00)	Z = -9.35	< 0.001
PIVKA-II (mAU/mL)	33.85 (20.89, 1839.88)	22.59 (16.30, 32.28)	854.40 (37.98, 14001.70)	Z = -11.58	< 0.001
CEA (ng/mL)	2.21 (1.35, 3.36)	2.08 (1.28, 3.39)	2.27 (1.42, 3.36)	Z = -1.41	0.16
CA199 (ng/mL)	19.75 (10.60, 38.92)	18.07 (9.85, 34.82)	21.25 (12.70, 43.17)	Z = -1.58	0.115
CA125 (ng/mL)	23.91 (12.77, 103.25)	33.51 (14.52, 143.25)	19.70 (12.24, 55.62)	Z = -3.05	0.002
Sex, n (%)				χ² = 9.90	0.002
Male	288 (75.39)	130 (68.42)	158 (82.29)
Female	94 (24.61)	60 (31.58)	34 (17.71)

WBC: White blood cell; RBC: Red blood cell; HB: Hemoglobin level; PLT: Platelet; AFP: Alpha-fetoprotein; PIVKA-II: Protein induced by vitamin K absence or antagonist II; CEA: Carcinoembryonic antigen; CA: Carbohydrate antigen; HCC: Hepatocellular carcinoma.

Table 3 Performance of modeling indicators and prediction models in the diagnosis of hepatocellular carcinoma

Variables	AUC (95%CI)	Cut-off	Accuracy (%)	Se (%)	Sp (%)	PPV (%)	NPV (%)	F1 Score
Age	0.638 (0.582, 0.693)	53.50	62.57	59.90	65.26	63.54	61.69	0.62
WBC (109/L)	0.703 (0.651, 0.755)	4.10	67.54	65.63	69.47	68.48	66.67	0.67
RBC (1012/L)	0.653 (0.598, 0.708)	4.22	63.09	70.83	55.26	61.54	65.22	0.66
PLT (109/L)	0.735 (0.685, 0.785)	109.00	68.32	55.73	81.05	74.83	64.44	0.64
AFP (ng/mL)	0.776 (0.729, 0.823)	19.05	73.30	59.90	86.84	82.14	68.18	0.69
PIVKA-II (mAU/mL)	0.842 (0.802, 0.882)	90.91	79.32	69.79	88.95	86.45	74.45	0.77
LR-training set	0.850 (0.812, 0.888)	0.47	78.01	63.02	93.16	90.30	71.37	0.74
LR-validation set	0.827 (0.764, 0.890)	0.47	74.55	65.06	84.15	80.60	70.41	0.79
SVM-training set	0.860 (0.822, 0.898)	0.54	80.10	71.35	88.95	86.71	75.45	0.72
SVM-validation set	0.803 (0.735, 0.871)	0.54	72.73	68.67	76.83	75.00	70.79	0.77
RF-training set	0.969 (0.955, 0.984)	0.52	92.15	88.02	96.32	96.02	88.83	0.78
RF-validation set	0.858 (0.800, 0.917)	0.52	80.00	75.90	84.15	82.89	77.53	0.72
LASSO-training set	0.845 (0.806, 0.884)	0.18	78.80	69.27	88.42	85.81	74.01	0.72
LASSO-validation set	0.831 (0.769, 0.893)	0.18	72.73	68.67	76.83	75.00	70.79	0.81
ASAP-training set	0.866 (0.829, 0.903)	0.93	82.20	73.96	90.53	88.75	77.48	0.92
ASAP-validation set	0.813 (0.747, 0.879)	0.93	73.94	61.45	86.59	82.26	68.93	0.70

Se: Sensitivity; Sp: Specificity; PPV: Positive predictive value: NPV: Negative predictive value; AUC: Area under the curve; LASSO: Least absolute shrinkage and selection operator; LR: Logistic regression; SVM: Support vector machine; RF: Random forest; LASSO: Least absolute shrinkage and selection operator; AUC: Area under the curve; WBC: White blood cell; RBC: Red blood cell; PLT: Platelet; AFP: Alpha-fetoprotein; PIVKA-II: Protein induced by vitamin K absence or antagonist II.