Biparametric magnetic resonance imaging-based radiomic and deep learning models for predicting Ki-67 risk stratification in hepatocellular carcinoma

Table 1 Baseline characteristics of the included patients, n (%)/mean ± SD

		Total (n = 198)	Training (n = 138)	Validation (n = 60)	P value
Age (Years)		62.53 ± 10.39	62.27 ± 10.38	63.13 ± 10.47	0.624
Sex	Male	164 (82.83)	117 (84.78)	47 (78.33)	0.368
	Female	34 (17.17)	21 (15.22)	13 (21.67)
ALT (U/L)		35.96 ± 32.93	36.51 ± 35.22	34.70 ± 27.14	0.962
AST (U/L)		74.23 ± 44.00	71.43 ± 43.04	80.65 ± 45.87	0.189
TB (μmol/L)		16.38 ± 11.32	16.35 ± 12.90	16.46 ± 6.42	0.096
Cirrhosis	Positive	55 (27.78)	39 (28.26)	16 (26.67)	0.954
	Negative	143 (72.22)	99 (71.74)	44 (73.33)
AFP	≤ 20 ng/mL	106 (53.54)	77 (55.80)	29 (48.33)	0.416
	> 20 ng/mL	92 (46.46)	61 (44.20)	31 (51.67)
HBV/HCV	Positive	146 (73.74)	99 (71.74)	47 (78.33)	0.428
	Negative	52 (26.26)	39 (28.26)	13 (21.67)
BCLC stage	0-A	178 (89.90)	124 (89.86)	54 (90.00)	1.0
	BC	20 (10.10)	14 (10.14)	6 (10.00)
Child-Pugh	A	183 (92.42)	125 (90.58)	58 (96.67)	0.232
	B	15 (7.58)	13 (9.42)	2 (3.33)
HCC number	1	185 (93.43)	129 (93.48)	56 (93.33)	1.0
	2	13 (6.57)	9 (6.52)	4 (6.67)
Irregular shape	Positive	103 (52.02)	69 (50.00)	34 (56.67)	0.479
	Negative	95 (47.98)	69 (50.00)	26 (43.33)
Nonsmooth margin	Positive	117 (59.09)	83 (60.14)	34 (56.67)	0.764
	Negative	81 (40.91)	55 (39.86)	26 (43.33)
Enhancing capsule	Positive	168 (84.85)	120 (86.96)	48 (80.00)	0.299
	Negative	30 (15.15)	18 (13.04)	12 (20.00)
Mosaic architecture	Positive	115 (58.08)	84 (60.87)	31 (51.67)	0.294
	Negative	83 (41.92)	54 (39.13)	29 (48.33)
Peritumoral enhancement	Positive	82 (41.41)	58 (42.03)	24 (40.00)	0.913
	Negative	116 (58.59)	80 (57.97)	36 (60.00)
Intratumoral fat content	Positive	63 (31.82)	39 (28.26)	24 (40.00)	0.143
	Negative	135 (68.18)	99 (71.74)	36 (60.00)
Intratumoral blood products	Positive	72 (36.36)	49 (35.51)	23 (38.33)	0.827
	Negative	126 (63.64)	89 (64.49)	37 (61.67)
Ki-67 expression	Grade 1	119 (60.10)	78 (56.52)	41 (68.34)	0.196
	Grade 2	53 (26.77)	42 (30.44)	11 (18.33)
	Grade 3	26 (13.13)	18 (13.04)	8 (13.33)

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; TB: Total bilirubin; AFP: Alpha-fetoprotein; HBV: Hepatitis B virus; HCV: Hepatitis C virus; BCLC: Barcelona clinical liver cancer; HCC: Hepatocellular carcinoma.

Table 2 Differences in clinical factors between the high and low Ki-67 risk stratification groups, n (%)/mean ± SD

		Training (n = 138)			Validation (n = 60)
		High Ki-67 (n = 61)	Low Ki-67 (n = 77)	P value	High Ki-67 (n = 19)	Low Ki-67 (n = 41)	P value
Age (Years)		62.42 ± 8.46	62.08 ± 12.47	0.852	61.47 ± 9.64	63.90 ± 10.86	0.408
Sex	Male	53 (86.89)	64 (83.12)	0.709	16 (84.21)	31 (75.61)	0.678
	Female	8 (13.11)	13 (16.88)		3 (15.79)	10 (24.39)
ALT (U/L)		34.70 ± 30.76	38.80 ± 40.31	0.424	37.16 ± 21.46	33.57 ± 29.59	0.137
AST (U/L)		66.91 ± 44.02	77.15 ± 41.42	0.152	95.58 ± 37.20	73.73 ± 48.23	0.066
TB (μmol/L)		17.05 ± 15.31	15.46 ± 9.05	0.85	14.56 ± 4.06	17.34 ± 7.14	0.236
Tumor size (cm)		4.47 ± 2.68	5.20 ± 3.37	0.265	6.08 ± 3.56	4.88 ± 3.04	0.369
Cirrhosis	Positive	17 (27.87)	22 (28.57)	1.0	3 (15.79)	13 (31.71)	0.326
	Negative	44 (72.13)	55 (71.43)		16 (84.21)	28 (68.29)
AFP	≤ 20 ng/mL	25 (40.98)	52 (67.53)	0.003	5 (26.32)	24 (58.54)	0.041
	> 20 ng/mL	36 (59.02)	25 (32.47)		14 (73.68)	17 (41.46)
HBV/HCV	Positive	44 (72.13)	55 (71.43)	1.0	16 (84.21)	31 (75.61)	0.678
	Negative	17 (27.87)	22 (28.57)		3 (15.79)	10 (24.39)
BCLC stage	0-A	51 (83.61)	73 (94.81)	0.06	18 (94.74)	36 (87.80)	0.711
	B-C	10 (16.39)	4 (5.19)		1 (5.26)	5 (12.20)
Child-Pugh	A	55 (90.16)	70 (90.91)	1.0	18 (94.74)	40 (97.56)	1.0
	B	6 (9.84)	7 (9.09)		1 (5.26)	1 (2.44)
HCC number	0	58 (95.08)	71 (92.21)	0.74	19 (100.00)	37 (90.24)	0.394
	1-2	3 (4.92)	6 (7.79)		0 (0.00)	4 (9.76)
Irregular shape	Positive	25 (40.98)	44 (57.14)	0.087	5 (26.32)	21 (51.22)	0.126
	Negative	36 (59.02)	33 (42.86)		14 (73.68)	20 (48.78)
Nonsmooth margin	Positive	43 (70.49)	12 (15.58)	< 0.001	14 (73.68)	12 (29.27)	0.003
	Negative	18 (29.51)	65 (84.42)		5 (26.32)	29 (70.73)
Enhancing capsule	Positive	49 (80.33)	71 (92.21)	0.071	13 (68.42)	35 (85.37)	0.238
	Negative	12 (19.67)	6 (7.79)		6 (31.58)	6 (14.63)
Mosaic architecture	Positive	29 (47.54)	25 (32.47)	0.104	9 (47.37)	20 (48.78)	1.0
	Negative	32 (52.46)	52 (67.53)		10 (52.63)	21 (51.22)
Peritumoral enhancement	Positive	33 (54.10)	25 (32.47)	0.017	9 (47.37)	15 (36.59)	0.61
	Negative	28 (45.90)	52 (67.53)		10 (52.63)	26 (63.41)
Intratumoral fat content	Positive	15 (24.59)	24 (31.17)	0.508	9 (47.37)	15 (36.59)	0.61
	Negative	46 (75.41)	53 (68.83)		10 (52.63)	26 (63.41)
Intratumoral blood products	Positive	22 (36.07)	27 (35.06)	1.0	10 (52.63)	13 (31.71)	0.206
	Negative	39 (63.93)	50 (64.94)		9 (47.37)	28 (68.29)

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; TB: Total bilirubin; AFP: Alpha-fetoprotein; HBV: Hepatitis B virus; HCV: Hepatitis C virus; BCLC: Barcelona Clinical Liver Cancer; HCC: Hepatocellular carcinoma.

Table 3 Univariable and multivariable analyses for high Ki-67 risk stratification

	Univariate analysis			Multivariate analysis
	OR	95%CI	P value	OR	95%CI	P value
Age	0.99	0.99-1.00	0.170
Sex	0.83	0.61-1.12	0.310
ALT	0.99	0.99-1.00	0.609
AST	0.99	0.99-1.00	0.649
TB	0.99	0.97-1.00	0.139
Cirrhosis	0.77	0.45-1.31	0.425
AFP	1.44	0.94-2.21	0.161
HBV/HCV	0.80	0.57-1.12	0.270
BCLC stage	2.50	0.95-6.61	0.121
Child-Pugh	0.86	0.34-2.14	0.782
HCC number	0.79	0.61-1.03	0.141
Irregular shape	1.09	0.73-1.62	0.718
Nonsmooth margin	3.58	2.09-6.13	< 0.001	11.06	5.60-21.82	< 0.001
Enhancing capsule	0.69	0.51-0.94	0.046	0.27	0.17-0.42	< 0.001
Mosaic architecture	1.16	0.74-1.82	0.587
Intratumoral fat content	0.63	0.36-1.08	0.153
Intratumoral blood products	0.82	0.51-1.31	0.476
Peritumoral enhancement	1.32	0.85-2.04	0.295

OR: Odds ratio; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; TB: Total bilirubin; AFP: Alpha-fetoprotein; HBV: Hepatitis B virus; HCV: Hepatitis C virus; BCLC: Barcelona Clinical Liver Cancer; HCC: Hepatocellular carcinoma.

Table 4 Diagnostic value of the different models in predicting high Ki-67 risk stratification in hepatocellular carcinoma patients

Model	Number of features	Group	Accuracy	Recall	F1	AUC (95%CI)	Sensitivity	Specificity
Clinical	2	Training	0.78	0.705	0.741	0.77 (0.70-0.84)	0.71	0.84
		Validation	0.72	0.737	0.622	0.72 (0.60-0.85)	0.74	0.71
Radiomics	10	Training	0.75	0.705	0.711	0.81 (0.74-0.88)	0.71	0.78
		Validation	0.75	0.474	0.545	0.65 (0.50-0.81)	0.47	0.88
DTL	25	Training	0.80	0.787	0.774	0.87 (0.81-0.92)	0.79	0.81
		Validation	0.57	0.895	0.567	0.67 (0.53-0.82)	0.90	0.42
Nomogram	4	Training	0.84	0.918	0.836	0.92 (0.88-0.97)	0.78	0.95
		Validation	0.68	0.842	0.627	0.75 (0.60-0.88)	0.84	0.61

DTL: Deep transfer learning; AUC: Area under the curve.