Machine learning model using immune indicators to predict outcomes in early liver cancer

Table 1 Baseline demographics and clinical characteristics of patients with hepatocellular carcinoma in the training and validation cohorts, n (%)

Variables	Total (n = 808)	Training group (n = 539)	Validation group (n = 269)	P values
Patients background
Gender, male/female	602/206	399/140	203/66	0.721
Age, year (Q1, Q3)	56 (50, 62)	56 (50, 62)	56 (50, 63)	0.575
Cirrhosis	665 (82.20)	438 (81.26)	227 (84.38)	0.318
Decompensation	445 (55.07)	286 (53.09)	159 (59.10)	0.12
Smoking	340 (42.07)	215 (39.88)	125 (46.46)	0.087
Drinking	334 (41.33)	221 (41.00)	113 (42.00)	0.843
Family history of HCC	80 (9.90)	57 (10.57)	23 (8.55)	0.433
Diabetes	176 (21.78)	109 (20.22)	67 (24.90)	0.153
Hypertension	223 (27.59)	145 (26.90)	78 (28.99)	0.586
Antiviral	477 (59.03)	315 (58.44)	162 (60.22)	0.682
Ascites				0.106
Mild ascites	181 (22.40)	111 (20.59)	70 (26.02)
Severe ascites	51 (6.31)	40 (7.42)	11 (4.08)
HE	13 (1.61)	7 (1.29)	6 (2.23)	0.377
UGIB	32 (3.96)	21 (3.89)	11 (4.08)	0.856
Laboratory parameters
ALT, U/L, (Q1, Q3)	27.8 (19, 41.95)	28 (19.1, 42.5)	27.2 (18.9, 41)	0.529
AST, U/L, (Q1, Q3)	30.1 (22.8, 44.15)	30.1 (23.1, 44.2)	30.1 (22.5, 43.3)	0.95
TBIL, μmol/L, (Q1, Q3)	15.6 (10.8, 23)	15.9 (11.1, 22.95)	13.9 (10.3, 23.4)	0.114
PLR, (Q1, Q3)	80.5 (59.68, 111.43)	82.02 (59.65, 112.63)	79.01 (59.89, 107.34)	0.352
NLR, (Q1, Q3)	1.92 (1.4, 2.84)	1.91 (1.4, 2.78)	1.92 (1.4, 2.95)	0.548
LMR, (Q1, Q3)	3.63 (2.59, 4.83)	3.61 (2.59, 4.72)	3.67 (2.59, 5)	0.48
ALBI
I	369 (45.66)	248 (46.01)	121 (45.12)	0.866
II	387 (47.89)	258 (47.86)	129 (46.95)
III	52 (6.43)	33 (6.12)	19 (7.06)
Child-Pugh				0.233
Grade A	656 (81.18)	445 (82.56)	211 (78.43)
Grade B	152 (18.81)	94 (17.43)	58 (21.56)
CRP, mg/L	4.2 (1.5, 12.55)	4.2 (1.5, 12.1)	4.5 (1.5, 13.28)	0.665
ALB, g/L, (Q1, Q3)	38.35 (33.27, 42.3)	38.7 (33.45, 42.4)	37.9 (33.1, 42.1)	0.278
GLB, g/L, (Q1, Q3)	30.2 (26.8, 34.23)	30.1 (26.85, 34.1)	30.3 (26.5, 34.8)	0.929
LDH, U/L, (Q1, Q3)	173.35 (149.88, 201.77)	173.5 (149.8, 203.3)	173.2 (150, 196.6)	0.59
Cr, μmol/L, (Q1, Q3)	0.76 (0.66, 0.87)	0.76 (0.64, 0.87)	0.77 (0.67, 0.9)	0.076
HBV-DNA ≥ 250, IU/mL	287 (35.51)	205 (38.03)	82 (30.48)	0.05
Tumor-related indicators
AFP ≥ 400, ng/mL	133 (16.36)	90 (16.69)	43 (15.98)	0.875
Tumor size, ≥ 2 cm	340 (42.07)	232 (43.04)	108 (40.14)	0.478
Tumor multiplicity				0.96
Solidary	726 (89.85)	485 (89.98)	241 (89.59)
Multiple	82 (10.14)	54 (10.02)	28 (10.41)
BCLC				0.546
BCLC 0	43 (5.32)	31 (5.75)	12 (4.46)
BCLC A	765 (94.67)	508 (94.25)	257 (95.54)
Etiology
HBV-infection	630 (77.97)	420 (77.92)	210 (78.06)	0.965
HCV-infection	68 (8.41)	47 (8.71)	21 (7.80)	0.759
AH	71 (8.78)	43 (7.97)	28 (10.40)	0.308
Other	39 (4.82)	29 (5.38)	10 (3.71)	0.387

Data are presented as n (%), or median (interquartile range). HCC: Hepatocellular carcinoma; HE: Hepatic encephalopathy; UGIB: Upper Gastrointestinal Bleeding; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; TBIL: Total bilirubin; PLR: Platelet-to-lymphocyte ratio; NLR: Neutrophil-to-lymphocyte ratio; LMR: Lymphocyte-to-monocyte ratio; ALBI: Albumin-bilirubin; CRP: C-reactive protein; ALB: Albumin; GLB: Globulin; LDH: Lactate dehydrogenase; Cr: Creatinine; HBV: Hepatitis B virus; AFP: Alpha-Fetoprotein; BCLC: Barcelona Clinic Liver Cancer Staging; HCV: Hepatitis C virus; AH: Alcoholic hepatitis.

Table 2 Comparison of the performance and discriminative ability between the artificial neural networks model and conventional models

Corhort	Models	1-year AUROC (95%CI)	3-year AUROC (95%CI)	5-year AUROC (95%CI)	C-index
Training	ANN	0.92 (0.88-0.95)	0.87 (0.84-0.91)	0.85 (0.82-0.88)	0.81
	JIS	0.77 (0.70-0.83)	0.71 (0.65-0.78)	0.65 (0.61-0.70)	0.63
	Okuda	0.61 (0.53-0.69)	0.70 (0.65-0.75)	0.66 (0.62-0.70)	0.64
	CUPI	0.75 (0.66-0.83)	0.71 (0.63-0.87)	0.73 (0.69-0.77)	0.68
	CLIP	0.71 (0.63-0.78)	0.73 (0.68-0.78)	0.70 (0.66-0.74)	0.66
Validation	ANN	0.81 (0.71-0.91)	0.79 (0.71-0.87)	0.82 (0.74-0.85)	0.78
	JIS	0.60 (0.50-0.73)	0.66 (0.56-0.76)	0.61 (0.54-0.68)	0.61
	Okuda	0.67 (0.55-0.80)	0.69 (0.60-0.79)	0.69 (0.63-0.76)	0.63
	CUPI	0.78 (0.71-0.85)	0.75 (0.69-0.82)	0.76 (0.70-0.82)	0.68
	CLIP	0.70 (0.59-0.81)	0.71 (0.63-0.79)	0.72 (0.66-0.78)	0.66

ANN: Artificial neural network; RSF: Random survival forest; JIS: Japan integrated staging score; Okuda: Okuda staging system; CUPI: Chinese university prognostic index; CLIP: Cancer of the liver Italian program; AUROC: Area under the receiver operating characteristic.