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©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
Published online Aug 27, 2024. doi: 10.4254/wjh.v16.i8.1131
Table 1 Clinicopathological features of patients with hepatocellular carcinoma
Variable | n | Percentage (%) |
Total | 182 | 100.0 |
Age (years)1 | ||
< 49 | 98 | 53.8 |
≥ 49 | 84 | 46.2 |
Gender | ||
Male | 135 | 74.2 |
Female | 47 | 25.8 |
Race | ||
Han | 89 | 48.9 |
Others | 93 | 51.1 |
Smoking | ||
No | 138 | 75.8 |
Yes | 44 | 24.2 |
Drinking | ||
No | 135 | 74.2 |
Yes | 47 | 25.8 |
HBsAg | ||
Negative | 63 | 34.6 |
Positive | 119 | 65.4 |
Anti-HCV | ||
Negative | 149 | 81.9 |
Positive | 33 | 18.1 |
AFP | ||
Negative | 64 | 35.2 |
Positive | 118 | 64.8 |
AFB1 exposure | ||
Low | 75 | 41.2 |
High | 107 | 58.8 |
Tumor size | ||
≤ 5 cm | 56 | 30.8 |
> 5 cm | 126 | 69.2 |
ES grade | ||
Low | 94 | 51.6 |
High | 88 | 48.4 |
TNM stage | ||
I | 30 | 16.5 |
II | 78 | 42.9 |
III | 74 | 40.7 |
Liver cirrhosis | ||
No | 56 | 30.8 |
Yes | 126 | 69.2 |
MVD | ||
Low | 90 | 49.5 |
High | 92 | 50.5 |
PVTT | ||
Negative | 127 | 69.8 |
Positive | 55 | 30.2 |
MVI | ||
Negative | 116 | 63.7 |
Positive | 66 | 36.3 |
Table 2 Clinical pathological features of hepatocellular carcinoma according to tissue inhibitor of metalloproteinase-3 expression
Variable | LTE | n | HTE | |||
n | Percentage (%) | Percentage (%) | P value | |||
Total | 89 | 100.0 | 93 | 100.0 | ||
Age (years) | 0.78 | |||||
< 49 | 47 | 52.8 | 51 | 54.8 | ||
≥ 49 | 42 | 47.2 | 42 | 45.2 | ||
Gender | 0.18 | |||||
Male | 70 | 78.7 | 65 | 69.9 | ||
Female | 19 | 21.3 | 28 | 30.1 | ||
Race | 0.89 | |||||
Han | 44 | 49.4 | 45 | 48.4 | ||
Others | 45 | 50.6 | 48 | 51.6 | ||
Smoking | 0.38 | |||||
No | 70 | 78.7 | 68 | 73.1 | ||
Yes | 19 | 21.3 | 25 | 26.9 | ||
Drinking | 0.50 | |||||
No | 68 | 76.4 | 67 | 72.0 | ||
Yes | 21 | 23.6 | 26 | 28.0 | ||
HBsAg | 0.13 | |||||
Negative | 26 | 29.2 | 37 | 39.8 | ||
Positive | 63 | 70.8 | 56 | 60.2 | ||
Anti-HCV | 0.47 | |||||
Negative | 71 | 79.8 | 78 | 83.9 | ||
Positive | 18 | 20.2 | 15 | 16.1 | ||
AFP | 4.66 × 10-13 | |||||
Negative | 8 | 9.0 | 56 | 60.2 | ||
Positive | 81 | 91.0 | 37 | 39.8 | ||
Tumor size | 2.54 × 10-4 | |||||
≤ 5 cm | 16 | 18.0 | 40 | 43.0 | ||
> 5 cm | 73 | 82.0 | 53 | 57.0 | ||
ES grade | 3.84 × 10-4 | |||||
Low | 34 | 38.2 | 60 | 64.5 | ||
High | 55 | 61.8 | 33 | 35.4 | ||
TNM stage | 1.18 × 10-4 | |||||
I | 6 | 6.7 | 24 | 25.8 | ||
II | 35 | 39.3 | 43 | 46.2 | ||
III | 48 | 53.9 | 26 | 28.0 | ||
Liver cirrhosis | 0.14 | |||||
No | 32 | 36.0 | 24 | 25.8 | ||
Yes | 57 | 64.0 | 69 | 74.2 | ||
MVD | 2.97 × 10-3 | |||||
Low | 34 | 38.2 | 56 | 60.2 | ||
High | 55 | 61.8 | 37 | 39.8 | ||
PVTT | 2.32 × 10-5 | |||||
Negative | 49 | 55.1 | 78 | 83.9 | ||
Positive | 40 | 44.9 | 15 | 16.1 | ||
MVI | 2.99 × 10-4 | |||||
Negative | 45 | 50.6 | 71 | 76.3 | ||
Positive | 44 | 49.4 | 22 | 23.7 |
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 AFP | 15.32 | 6.63-35.38 | 1.65 × 10-10 |
Higher tumor size | 3.47 | 1.75-6.87 | 3.69 × 10-4 |
Tumor dedifferentiation | 3.04 | 1.65-5.65 | 4.31 × 10-4 |
Higher TNM stage | 2.60 | 1.64-4.07 | 4.21 × 10-5 |
Higher MVD | 2.45 | 1.35-4.45 | 3.20 × 10-3 |
Higher risk of PVTT | 4.38 | 2.18-8.83 | 3.52 × 10-4 |
Higher risk of MVI | 3.24 | 1.71-6.14 | 3.20 × 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) | 0.71 | 0.97 | ||||
< 49 | 79 (80.6) | 27.00 (22.12-31.88) | 68 (69.4) | 27.00 (20.88-33.12) | ||
≥ 49 | 71 (84.5) | 23.00 (19.04-26.96) | 56 (66.7) | 24.00 (18.84-29.16) | ||
Gender | 0.68 | 0.55 | ||||
Male | 113 (83.7) | 26.00 (2299-29.01) | 91 (67.4) | 24.00 (17.96-30.05) | ||
Female | 37 (78.7) | 26.00 (21.71-30.29) | 33 (70.2) | 25.00 (17.96-30.04) | ||
Race | 0.76 | 0.26 | ||||
Han | 74 (83.1) | 27.00 (22.55-31.76) | 65 (73.0) | 25.00 (19.01-30.99) | ||
Others | 76 (81.7) | 26.00 (21.88-30.81) | 59 (63.4) | 25.00 (15.63-34.37) | ||
Smoking | 0.06 | 0.01 | ||||
No | 114 (82.6) | 24.00 (20.33-27.67) | 101 (73.2) | 24.00 (18.62-29.38) | ||
Yes | 36 (81.8) | 27.00 (19.67-34.43) | 23 (52.3) | 33.00 (15.27-50.74) | ||
Drinking | 0.10 | 0.03 | ||||
No | 110 (81.5) | 24.00 (20.17-27.83) | 97 (71.9) | 24.00 (18.44-29.56) | ||
Yes | 40 (85.1) | 27.00 (22.53-31.47) | 27 (57.4) | 30.00 (15.73-44.27) | ||
HBsAg | 0.26 | 0.05 | ||||
Negative | 44 (69.8) | 28.00 (24.38-31.62) | 34 (54.0) | 29.00 (18.01-40.00) | ||
Positive | 106 (89.1) | 24.00 (19.47-28.53) | 90 (75.6) | 22.00 (16.52-27.48) | ||
Anti-HCV | 0.45 | 0.88 | ||||
Negative | 123 (82.6) | 24.00 (19.69-28.31) | 99 (66.4) | 24.00 (17.81-30.19) | ||
Positive | 27 (81.8) | 28.00 (23.80-32.20) | 25 (75.8) | 28.00 (20.61-35.39) | ||
AFP | 1.85 × 10-9 | 1.03 × 10-6 | ||||
Negative | 44 (68.7) | 41.00 (29.46-52.54) | 35 (54.7) | 40.00 (30.18-49.82) | ||
Positive | 106 (89.8) | 20.00 (17.24-22.77) | 89 (75.4) | 17.00 (13.10-20.90) | ||
AFB1 exposure | 1.31 × 10-9 | 9.39 × 10-10 | ||||
Low | 58 (77.3) | 36.00 (26.75-45.25) | 38 (50.7) | 43.00 (33.01-52.99) | ||
High | 92 (86.0) | 20.00 (17.22-22.78) | 86 (80.4) | 18.00 (14.25-21.75) | ||
Tumor size | 5.52 × 10-8 | 5.3 × 10-6 | ||||
≤ 5 cm | 37 (66.1) | 39.00 (27.27-50.73) | 31 (55.4) | 40.00 (31.01-48.99) | ||
> 5 cm | 113 (89.7) | 19.00 (15.84-22.16) | 93 (73.8) | 16.00 (12.48-19.52) | ||
ES grade | 3.82 × 10-4 | 9.07 × 10-3 | ||||
Low | 75 (79.8) | 33.00 (28.08-37.92) | 61 (64.9) | 30.00 (25.23-34.77) | ||
High | 75 (85.2) | 20.00 (17.07-22.93) | 63 (71.6) | 19.00 (13.83-24.17) | ||
TNM stage | 7.40 × 10-17 | 4.47 × 10-11 | ||||
I | 24 (80.0) | 45.00 (35.63-54.37) | 19 (63.3) | 37.00 (28.77-45.23) | ||
II | 59 (75.6) | 27.00 (23.79-30.21) | 47 (60.3) | 29.00 (21.89-36.11) | ||
III | 67 (90.5) | 12.00 (8.63-15.37) | 58 (78.4) | 10.00 (6.26-13.75) | ||
Liver cirrhosis | 0.93 | 0.43 | ||||
No | 45 (80.4) | 27.00 (21.49-32.52) | 34 (60.7) | 27.00 (21.56-32.44) | ||
Yes | 105 (83.3) | 25.00 (21.51-28.49) | 90 (71.4) | 24.00 (19.69-28.31) | ||
MVD | 7.60 × 10-11 | 1.07 × 10-11 | ||||
Low | 68 (75.6) | 34.00 (31.65-36.35) | 49 (54.4) | 36.00 (27.49-44.51) | ||
High | 82 (89.1) | 15.00 (11.87-18.13) | 75 (81.5) | 13.00 (9.00-16.01) | ||
PVTT | 1.50 × 10-6 | 9.99 × 10-7 | ||||
Negative | 103 (81.1) | 29.00 (24.61-33.39) | 80 (63.0) | 30.00 (25.71-34.29) | ||
Positive | 47 (85.5) | 12.00 (7.96-16.04) | 44 (80.0) | 8.00 (5.09-10.91) | ||
MVI | 6.65 × 10-8 | 1.55 × 10-7 | ||||
Negative | 95 (81.9) | 29.00 (24.69-33.31) | 73 (62.9) | 30.00 (25.90-34.10) | ||
Positive | 55 (83.3) | 11.00 (6.66-15.34) | 51 (77.3) | 8.00 (4.38-11.62) | ||
TIMP3 | 3.91 × 10-11 | 1.89 × 10-6 | ||||
LTE | 86 (96.6) | 18.00 (16.64-21.36) | 70 (78.7) | 16.00 (12.31-19.69) | ||
HTE | 64 (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 < 49 | 1.06 (0.77-1.47) | 0.72 | 1.01 (0.71-1.44) | 0.97 |
Gender, male vs female | 0.93 (0.64-1.35) | 0.68 | 0.89 (0.59-1.32) | 0.55 |
Race, Han vs others | 0.95 (0.69-1.31) | 0.76 | 0.80 (0.58-1.32) | 0.27 |
Smoking, yes vs no | 0.70 (0.48-1.03) | 0.07 | 0.57 (0.36-0.89) | 0.01 |
Drinking, yes vs no | 0.74 (0.51-1.07) | 0.11 | 0.63 (0.41-0.96) | 0.03 |
HBV, positive vs negative | 1.22 (0.86-1.74) | 0.27 | 1.48 (0.99-2.19) | 0.05 |
HCV, positive vs negative | 0.85 (0.56-1.30) | 0.46 | 0.97 (0.62-1.50) | 0.89 |
AFP, positive vs negative | 2.93 (2.03-4.24) | 1.18 × 10-8 | 2.63 (1.75-3.95) | 3.04 × 10-6 |
AFB1 exposure, high vs low | 3.00 (2.06-4.36) | 8.43 × 10-9 | 3.41 (2.25-5.18) | 8.67 × 10-9 |
Tumor size (cm), > 5 vs ≤ 5 | 2.70 (1.85-3.93) | 2.63 × 10-7 | 2.50 (1.65-3.77) | 1.37 × 10-5 |
ES grade, III-IV vs I-II | 1.79 (1.29-2.49) | 5.55 × 10-4 | 1.60 (0.79-2.30) | 0.01 |
TNM stage, II vs I | 1.57 (0.97-2.53) | 0.06 | 1.35 (0.79-2.30) | 0.27 |
TNM stage, III vs I | 5.95 (3.56-9.94) | 1.01 × 10-11 | 4.29 (2.48-7.41) | 1.92 × 10-7 |
Liver cirrhosis, yes vs no | 1.02 (0.72-1.44) | 0.93 | 1.17 (0.79-1.74) | 0.43 |
MVD, high vs low | 2.87 (2.06-4.02) | 6.84 × 10-10 | 3.40 (2.34-4.96) | 1.82 × 10-10 |
PVTT, positive vs negative | 2.30 (1.62-3.28) | 4.06 × 10-6 | 2.43 (1.68-3.53) | 2.95 × 10-6 |
MVI, positive vs negative | 2.48 (1.75-3.50) | 2.56 × 10-7 | 2.53 (1.76-3.64) | 5.63 × 10-7 |
TIMP3, LTE vs HTE | 2.92 (2.19-4.09) | 4.10 × 10-10 | 2.34 (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) |
AETE1 | 47.00 (43.20-50.80) | 1.00 | 49.98 (42.03-57.93)1 | 1.00 |
AETE2 | 28.00 (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) |
AETE3 | 26.00 (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) |
AETE4 | 16.00 (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 negative | 2.85 (1.96-4.15) | 5.06 × 10-8 | 2.48 (1.64-3.73) | 1.44 × 10-5 |
AFB1 exposure, high vs low | 2.92 (1.99-4.27) | 3.71 × 10-8 | 3.23 (2.12-4.94) | 5.78 × 10-8 |
Tumor size (cm), > 5 vs ≤ 5 | 2.93 (1.99-4.31) | 4.53 × 10-8 | 2.79 (1.83-4.25) | 2.00 × 10-6 |
ES grade, III-IV vs I-II | 1.81 (1.29-2.55) | 6.19 × 10-4 | 1.63 (1.12-2.37) | 0.01 |
TNM stage, II vs I | 1.61 (1.02-2.42) | 0.03 | 1.75 (1.04-2.45) | 0.02 |
TNM stage, III vs I | 6.22 (3.70-10.48) | 6.21 × 10-12 | 4.43 (2.54-7.71) | 1.47 × 10-7 |
MVD, positive vs negative | 2.88 (2.05-4.04) | 1.07 × 10-9 | 3.34 (2.29-4.89) | 4.71 × 10-10 |
PVTT, positive vs negative | 2.30 (1.59-3.32) | 8.73 × 10-6 | 2.34 (1.60-3.42) | 1.16 × 10-5 |
MVI, positive vs negative | 2.48 (1.74-3.54) | 5.63 × 10-7 | 2.44 (1.68-3.53) | 2.42 × 10-6 |
TIMP3, LTE vs HTE | 2.85 (2.04-4.00) | 1.17 × 10-9 | 2.26 (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 | r | P value | |||
n | Percentage (%) | n | Percentage (%) | |||
LTE | 27 | 36.0 | 62 | 57.9 | -0.216 | 0.003 |
HTE | 48 | 64.0 | 45 | 42.1 |
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Citation: Liang QJ, Long QQ, Tian FQ, Su QY, Zhu XY, Long XD. Tissue inhibitor of metalloproteinase-3 expression affects clini
copathological features and prognosis of aflatoxin B1-related hepatocellular carcinoma. World J Hepatol 2024; 16(8): 1131-1144 - URL: https://www.wjgnet.com/1948-5182/full/v16/i8/1131.htm
- DOI: https://dx.doi.org/10.4254/wjh.v16.i8.1131