Development of a nomogram for predicting liver transplantation prognosis in hepatocellular carcinoma

Table 1 Characteristics of hepatocellular carcinoma patients, n (%)

Variables	Value
Gender (male/female)	147 (91.9)/13 (8.1)
Age, yr (≤ 50/> 50)	69 (43.1)/91 (56.9)
OS status (survive/dead)	105 (65.5)/55 (34.5)
RFS status (survive/relapsed)	104 (65.0)/56 (35.0)
ALT, U/L (≤ 40/> 40)	91 (56.9)/69 (43.1)
AST, U/L (≤ 40/> 40)	61 (38.1)/99 (61.9)
ALP, U/L (≤ 125/> 125)	108 (67.5)/52 (32.5)
GGT, U/L (≤ 60/> 60)	55 (34.4)/105 (65.6)
AFP, ng/mL (≤ 200/200-1000/> 1000)	107 (66.9)/19 (11.8)/34 (21.3)
GP73, ng/mL (≤ 150/> 150)	84 (52.5)/76 (47.5)
DCP, ng/mL (≤ 40/> 40)	96 (60.0)/64 (40.0)
CK18-M65, U/L (≤ 500/> 500)	48 (30.0)/112 (70.0)
CK18-M30, U/L (≤ 500/> 500)	91 (56.9)/69 (43.1)
Pathological diferentiation (well/moderate/poor)	9 (5.6)/127 (79.4)/24 (15.0)
Number of tumours (solitary/multiple)	79 (49.4)/81 (50.6)
Maximum tumor diameter, cm (≤ 5/> 5)	112 (70.0)/48 (30.0)
Total tumor diameter, cm (≤ 8/> 8)	114 (71.3)/46 (28.7)
Vascular invasion (yes/no)	42 (26.2)/118 (73.8)
Lymph node metastasis (yes/no)	20 (12.5)/140 (87.5)
Membrane invasion (yes/no)	51 (31.9)/109 (68.1)
Microsatellite lesions (yes/no)	79 (49.4)/81 (50.6)
Child-Pugh score (≤ 8/> 8)	116 (71.5)/44 (27.5)
MELD score (≤ 20/> 20)	147 (91.9)/13 (8.1)
Milan (yes/no)	64 (40.0)/96 (60.0)
UCSF (yes/no)	77 (48.1)/83 (51.9)
Hangzhou (yes/no)	109 (68.1)/51 (31.9)

DCP: Des-gamma-carboxy prothrombin; ALT: Alanine transaminase; AST: Aspartate transaminase; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transferase; DCP: Des-gamma-carboxy prothrombin; GP73: Golgi protein 73; OS: Overall survival; RFS: Recurrence free survival.

Table 2 The efficacy analysis of biomarkers

Variable	Cut-off	Specificity	Sensitivity	Positive rate	AUC	P value
AFP	400 ng/m L	87%	56%	28%	0.72	< 0.001
DCP	26 ng/m L	71%	69%	42%	0.71	< 0.001
GP73	222 ng/m L	87%	38%	21%	0.62	0.009
CK18-M65	1066 U/L	73%	67%	41%	0.72	< 0.001
CK18-M30	530 U/L	75%	71%	41%	0.73	< 0.001

AUC: Area under the curve; CK18: Cytokeratin-18; DCP: Des-gamma-carboxy prothrombin; GP73: Golgi protein 73; AFP: Alpha-fetoprotein; CK18: Cytokeratin-18.

Table 3 Univariate analysis for overall survival and recurrence-free survival

Variable	n	Overall survival (%)			P value	Recurrence-free survival (%)			P value
		1 yr	3 yr	5 yr		1 yr	3 yr	5 yr
Number of tumour					0.054				0.006
Single tumor	79	0.87	0.78	0.75		0.78	0.77	0.75
Multiple tumors	81	0.88	0.64	0.57		0.69	0.55	0.54
Maximum tumor diameter (cm)					< 0.001				< 0.001
> 5	48	0.79	0.50	0.43		0.58	0.45	-
≤ 5	112	0.92	0.80	0.73		0.80	0.75	0.73
Total tumor diameter (cm)					< 0.001				< 0.001
> 8	46	0.74	0.43	0.38		0.43	0.37	0.34
≤ 8	114	0.93	0.82	0.76		0.86	0.78	-
Vascular invasion					< 0.001				< 0.001
Yes	42	0.69	0.50	0.37		0.50	0.33	0.31
No	118	0.90	0.79	0.74		0.82	0.78	-
Lymph node metastasis					0.098				0.129
Yes	20	0.75	0.60	0.49		0.60	0.50	-
No	140	0.92	0.72	0.68		0.75	0.68	0.67
Membrane invasion					0.001				< 0.001
Yes	59	0.78	0.54	0.50		0.76	0.52	0.46
No	101	0.92	0.78	0.72		0.95	0.82	0.76
Microsatellite lesions					0.002				0.001
Yes	79	0.83	0.60	0.52		0.65	0.53	0.51
No	81	0.92	0.81	0.77		0.81	0.79	0.77
AFP					< 0.001				< 0.001
≤ 400	115	0.90	0.82	0.78		0.86	0.79	-
> 400	45	0.82	0.42	0.33		0.42	0.31	0.28
GP73					0.001				< 0.001
≤ 222	126	0.91	0.76	0.73		0.78	0.73	0.72
> 222	34	0.76	0.52	0.34		0.55	0.38	-
DCP					< 0.001				< 0.001
≤ 26	92	0.91	0.82	0.81		0.85	0.82	0.81
> 26	68	0.83	0.55	0.44		0.57	0.42	0.41
CK18-M65 (U/L)					< 0.001				< 0.001
≤ 1066	95	0.93	0.84	0.81		0.85	0.80	0.80
> 1066	65	0.80	0.52	0.41		0.56	0.43	0.41
CK18-M30 (U/L)					< 0.001				<0.001
≤ 530	95	0.94	0.86	0.83		0.86	0.83	0.82
> 530	65	0.78	0.49	0.39		0.54	0.40	0.39
MC					< 0.001				< 0.001
Yes	64	0.97	0.86	0.82		0.88	0.83	0.81
No	96	0.82	0.61	0.55		0.63	0.54	0.53
UCSF					< 0.001				< 0.001
Yes	77	0.97	0.89	0.85		0.90	0.87	0.85
No	83	0.79	0.54	0.46		0.57	0.47	0.45
Hangzhou					< 0.001				< 0.001
Yes	109	0.95	0.83	0.78		0.86	0.81	0.80
No	51	0.80	0.45	0.37		0.47	0.33	0.31

CK18: Cytokeratin-18; GP73: Golgi protein 73.

Table 4 Multivariate Cox hazards analysis for overall survival

Variable	B	SE	HR	95%CI	P value
AFP > 400 ng/mL	1.22	0.28	3.38	1.95-5.88	< 0.001
CK18-M30 > 530 U/L	1.14	0.31	3.15	1.69-5.87	< 0.001
TTD > 8 cm	0.92	0.28	2.52	1.45-4.40	0.001

95%CI: 95% confidence interval; HR: Hazard ratio; CK18: Cytokeratin-18; AFP: Alpha-fetoprotein; TTD: Total tumor diameter; B: Regression coefficient; SE: Standard error.

Table 5 Multivariate Cox hazards analysis for recurrence-free survival

Variable	B	SE	HR	95%CI	P value
AFP > 400 ng/mL	1.45	0.28	4.28	2.47-7.40	< 0.001
CK18-M30 > 530 U/L	0.97	0.31	2.66	1.44-4.91	0.002
TTD > 8 cm	1.10	0.28	3.03	1.73-5.29	< 0.001

95%CI: 95% confidence interval; HR: Hazard ratio; CK18: Cytokeratin-18; AFP: Alpha-fetoprotein; TTD: Total tumor diameter; B: Regression coefficient; SE: Standard error.

Table 6 The area under the curve comparison of the nomogram with the other standards

	Overall survival				Recurrence-free survival
	Nomogram	Milan	UCSF	Hangzhou	Nomogram	Milan	UCSF	Hangzhou
t = 1-yr	0.78	0.66	0.70	0.72	0.86	0.65	0.72	0.73
t = 3-yr	0.85	0.65	0.71	0.71	0.88	0.66	0.73	0.73
t = 5-yr	0.87	0.67	0.72	0.73	0.91	0.68	0.74	0.76

Table 7 Division of the risk classification and 5-year survival rate

	Low risk	Middle risk	High risk
OS
Total points	0-98	100-198	215-315
5-yr survival rate	≥ 90%	70%-89%	≤ 30%
RFS
Total points	0-100	108-208	208-280
5-yr survival rate	≥ 90%	45%-89%	≤ 45%

OS: Overall survival; RFS: Recurrence free survival.