Observational Study
Copyright ©The Author(s) 2024.
World J Hepatol. Aug 27, 2024; 16(8): 1131-1144
Published online Aug 27, 2024. doi: 10.4254/wjh.v16.i8.1131
Table 1 Clinicopathological features of patients with hepatocellular carcinoma
Variable
n
Percentage (%)
Total182100.0
Age (years)1
< 499853.8
≥ 498446.2
Gender
Male13574.2
Female4725.8
Race
Han8948.9
Others9351.1
Smoking
No13875.8
Yes4424.2
Drinking
No13574.2
Yes4725.8
HBsAg
Negative6334.6
Positive11965.4
Anti-HCV
Negative14981.9
Positive3318.1
AFP
Negative6435.2
Positive11864.8
AFB1 exposure
Low7541.2
High10758.8
Tumor size
≤ 5 cm5630.8
> 5 cm12669.2
ES grade
Low9451.6
High8848.4
TNM stage
I3016.5
II7842.9
III7440.7
Liver cirrhosis
No5630.8
Yes12669.2
MVD
Low9049.5
High9250.5
PVTT
Negative12769.8
Positive5530.2
MVI
Negative11663.7
Positive6636.3
Table 2 Clinical pathological features of hepatocellular carcinoma according to tissue inhibitor of metalloproteinase-3 expression
VariableLTE
HTE
P value
n
Percentage (%)
n
Percentage (%)
Total89100.093100.0
Age (years)0.78
< 494752.85154.8
≥ 494247.24245.2
Gender0.18
Male7078.76569.9
Female1921.32830.1
Race0.89
Han4449.44548.4
Others4550.64851.6
Smoking0.38
No7078.76873.1
Yes1921.32526.9
Drinking0.50
No6876.46772.0
Yes2123.62628.0
HBsAg0.13
Negative2629.23739.8
Positive6370.85660.2
Anti-HCV0.47
Negative7179.87883.9
Positive1820.21516.1
AFP4.66 × 10-13
Negative89.05660.2
Positive8191.03739.8
Tumor size2.54 × 10-4
≤ 5 cm1618.04043.0
> 5 cm7382.05357.0
ES grade3.84 × 10-4
Low3438.26064.5
High5561.83335.4
TNM stage1.18 × 10-4
I66.72425.8
II3539.34346.2
III4853.92628.0
Liver cirrhosis0.14
No3236.02425.8
Yes5764.06974.2
MVD2.97 × 10-3
Low3438.25660.2
High5561.83739.8
PVTT2.32 × 10-5
Negative4955.17883.9
Positive4044.91516.1
MVI2.99 × 10-4
Negative4550.67176.3
Positive4449.42223.7
Table 3 The risk effects of tissue inhibitor of metalloproteinase-3 expression in the cancerous tissues on the clinicopathological features of hepatocellular carcinoma
Risk effects
ORLTE/HTG1
95%CI
P value
Higher AFP15.326.63-35.381.65 × 10-10
Higher tumor size3.471.75-6.873.69 × 10-4
Tumor dedifferentiation3.041.65-5.654.31 × 10-4
Higher TNM stage2.601.64-4.074.21 × 10-5
Higher MVD2.451.35-4.453.20 × 10-3
Higher risk of PVTT4.382.18-8.833.52 × 10-4
Higher risk of MVI3.241.71-6.143.20 × 10-4
Table 4 Univariable Kaplan-Meier survival analysis
OS
RFS

De, n (%)
MST (95%CI)
P value
Re, n (%)
MRT (95%CI)
P value
Age (years)0.710.97
< 4979 (80.6)27.00 (22.12-31.88)68 (69.4)27.00 (20.88-33.12)
≥ 4971 (84.5)23.00 (19.04-26.96)56 (66.7)24.00 (18.84-29.16)
Gender0.680.55
Male113 (83.7)26.00 (2299-29.01)91 (67.4)24.00 (17.96-30.05)
Female37 (78.7)26.00 (21.71-30.29)33 (70.2)25.00 (17.96-30.04)
Race0.760.26
Han74 (83.1)27.00 (22.55-31.76)65 (73.0)25.00 (19.01-30.99)
Others76 (81.7)26.00 (21.88-30.81)59 (63.4)25.00 (15.63-34.37)
Smoking0.060.01
No114 (82.6)24.00 (20.33-27.67)101 (73.2)24.00 (18.62-29.38)
Yes36 (81.8)27.00 (19.67-34.43)23 (52.3)33.00 (15.27-50.74)
Drinking0.100.03
No110 (81.5)24.00 (20.17-27.83)97 (71.9)24.00 (18.44-29.56)
Yes40 (85.1)27.00 (22.53-31.47)27 (57.4)30.00 (15.73-44.27)
HBsAg0.260.05
Negative44 (69.8)28.00 (24.38-31.62)34 (54.0)29.00 (18.01-40.00)
Positive106 (89.1)24.00 (19.47-28.53)90 (75.6)22.00 (16.52-27.48)
Anti-HCV0.450.88
Negative123 (82.6)24.00 (19.69-28.31)99 (66.4)24.00 (17.81-30.19)
Positive27 (81.8)28.00 (23.80-32.20)25 (75.8)28.00 (20.61-35.39)
AFP1.85 × 10-91.03 × 10-6
Negative44 (68.7)41.00 (29.46-52.54)35 (54.7)40.00 (30.18-49.82)
Positive106 (89.8)20.00 (17.24-22.77)89 (75.4)17.00 (13.10-20.90)
AFB1 exposure1.31 × 10-99.39 × 10-10
Low58 (77.3)36.00 (26.75-45.25)38 (50.7)43.00 (33.01-52.99)
High92 (86.0)20.00 (17.22-22.78)86 (80.4)18.00 (14.25-21.75)
Tumor size5.52 × 10-85.3 × 10-6
≤ 5 cm37 (66.1)39.00 (27.27-50.73)31 (55.4)40.00 (31.01-48.99)
> 5 cm113 (89.7)19.00 (15.84-22.16)93 (73.8)16.00 (12.48-19.52)
ES grade3.82 × 10-49.07 × 10-3
Low75 (79.8)33.00 (28.08-37.92)61 (64.9)30.00 (25.23-34.77)
High75 (85.2)20.00 (17.07-22.93)63 (71.6)19.00 (13.83-24.17)
TNM stage7.40 × 10-174.47 × 10-11
I24 (80.0)45.00 (35.63-54.37)19 (63.3)37.00 (28.77-45.23)
II59 (75.6)27.00 (23.79-30.21)47 (60.3)29.00 (21.89-36.11)
III67 (90.5)12.00 (8.63-15.37)58 (78.4)10.00 (6.26-13.75)
Liver cirrhosis0.930.43
No45 (80.4)27.00 (21.49-32.52)34 (60.7)27.00 (21.56-32.44)
Yes105 (83.3)25.00 (21.51-28.49)90 (71.4)24.00 (19.69-28.31)
MVD7.60 × 10-111.07 × 10-11
Low68 (75.6)34.00 (31.65-36.35)49 (54.4)36.00 (27.49-44.51)
High82 (89.1)15.00 (11.87-18.13)75 (81.5)13.00 (9.00-16.01)
PVTT1.50 × 10-69.99 × 10-7
Negative103 (81.1)29.00 (24.61-33.39)80 (63.0)30.00 (25.71-34.29)
Positive47 (85.5)12.00 (7.96-16.04)44 (80.0)8.00 (5.09-10.91)
MVI6.65 × 10-81.55 × 10-7
Negative95 (81.9)29.00 (24.69-33.31)73 (62.9)30.00 (25.90-34.10)
Positive55 (83.3)11.00 (6.66-15.34)51 (77.3)8.00 (4.38-11.62)
TIMP33.91 × 10-111.89 × 10-6
LTE86 (96.6)18.00 (16.64-21.36)70 (78.7)16.00 (12.31-19.69)
HTE64 (68.8)36.00 (28.20-43.81)54 (58.1)32.00 (22.79-41.21)
Table 5 Univariable Cox proportional hazard regression survival analysis
OS
RFS
Variable
HR (95%CI)
P value
HR (95%CI)
P value
Age (years), ≥ 49 vs < 491.06 (0.77-1.47)0.721.01 (0.71-1.44)0.97
Gender, male vs female0.93 (0.64-1.35)0.680.89 (0.59-1.32)0.55
Race, Han vs others0.95 (0.69-1.31)0.760.80 (0.58-1.32)0.27
Smoking, yes vs no0.70 (0.48-1.03)0.070.57 (0.36-0.89)0.01
Drinking, yes vs no0.74 (0.51-1.07)0.110.63 (0.41-0.96)0.03
HBV, positive vs negative1.22 (0.86-1.74)0.271.48 (0.99-2.19)0.05
HCV, positive vs negative0.85 (0.56-1.30)0.460.97 (0.62-1.50)0.89
AFP, positive vs negative2.93 (2.03-4.24)1.18 × 10-82.63 (1.75-3.95)3.04 × 10-6
AFB1 exposure, high vs low3.00 (2.06-4.36)8.43 × 10-93.41 (2.25-5.18)8.67 × 10-9
Tumor size (cm), > 5 vs ≤ 52.70 (1.85-3.93)2.63 × 10-72.50 (1.65-3.77)1.37 × 10-5
ES grade, III-IV vs I-II1.79 (1.29-2.49)5.55 × 10-41.60 (0.79-2.30)0.01
TNM stage, II vs I1.57 (0.97-2.53)0.061.35 (0.79-2.30)0.27
TNM stage, III vs I5.95 (3.56-9.94)1.01 × 10-114.29 (2.48-7.41)1.92 × 10-7
Liver cirrhosis, yes vs no1.02 (0.72-1.44)0.931.17 (0.79-1.74)0.43
MVD, high vs low2.87 (2.06-4.02)6.84 × 10-103.40 (2.34-4.96)1.82 × 10-10
PVTT, positive vs negative2.30 (1.62-3.28)4.06 × 10-62.43 (1.68-3.53)2.95 × 10-6
MVI, positive vs negative2.48 (1.75-3.50)2.56 × 10-72.53 (1.76-3.64)5.63 × 10-7
TIMP3, LTE vs HTE2.92 (2.19-4.09)4.10 × 10-102.34 (1.63-3.38)4.80 × 10-6
Table 6 Effects of aflatoxin B1 exposure and tissue inhibitor of metalloproteinase-3 expression on survival of patients with aflatoxin B1-related hepatocellular carcinoma
OS
RFS
Variable
MST (95%CI)
HR (95%CI/P value)
MRT (95%CI)
HR (95%CI/P value)
AETE147.00 (43.20-50.80)1.0049.98 (42.03-57.93)11.00
AETE228.00 (21.25-34.75)2.51 (1.48-4.24/6.44 × 10-4)37.00 (21.45-52.55)1.84 (0.95-3.57/0.07)
AETE326.00 (21.29-30.71)2.59 (1.53-4.40/4.04 × 10-4)28.00 (21.60-34.40)2.90 (1.63-5.15/2.86 × 10-4)
AETE416.00 (11.72-20.28)7.41 (4.49-12.23/4.77 × 10-15)12.00 (7.65-16.35)6.38 (3.68-11.05/3.85 × 10-11)
Table 7 Mulvariable Cox proportional hazard regression analysis for survival
OS
RFS
Variable
HR (95%CI)
P value
HR (95%CI)
P value
AFP, positive vs negative2.85 (1.96-4.15)5.06 × 10-82.48 (1.64-3.73)1.44 × 10-5
AFB1 exposure, high vs low2.92 (1.99-4.27)3.71 × 10-83.23 (2.12-4.94)5.78 × 10-8
Tumor size (cm), > 5 vs ≤ 52.93 (1.99-4.31)4.53 × 10-82.79 (1.83-4.25)2.00 × 10-6
ES grade, III-IV vs I-II1.81 (1.29-2.55)6.19 × 10-41.63 (1.12-2.37)0.01
TNM stage, II vs I1.61 (1.02-2.42)0.031.75 (1.04-2.45)0.02
TNM stage, III vs I6.22 (3.70-10.48)6.21 × 10-124.43 (2.54-7.71)1.47 × 10-7
MVD, positive vs negative2.88 (2.05-4.04)1.07 × 10-93.34 (2.29-4.89)4.71 × 10-10
PVTT, positive vs negative2.30 (1.59-3.32)8.73 × 10-62.34 (1.60-3.42)1.16 × 10-5
MVI, positive vs negative2.48 (1.74-3.54)5.63 × 10-72.44 (1.68-3.53)2.42 × 10-6
TIMP3, LTE vs HTE2.85 (2.04-4.00)1.17 × 10-92.26 (1.57-3.26)1.26 × 10-5
Table 8 Correlation between aflatoxin B1 exposure and tissue inhibitor of metalloproteinase-3 expression in hepatocellular carcinoma

Low AFB1 exposure
High AFB1 exposure
rP value
n
Percentage (%)
n
Percentage (%)
LTE2736.06257.9-0.2160.003
HTE4864.04542.1