Copyright
©The Author(s) 2016.
World J Gastroenterol. Apr 28, 2016; 22(16): 4168-4182
Published online Apr 28, 2016. doi: 10.3748/wjg.v22.i16.4168
Published online Apr 28, 2016. doi: 10.3748/wjg.v22.i16.4168
Table 1 Clinical data of the studied groups n (%)
HCC (n = 192) | Cirrhotic (n = 96) | Non-cirrhotic (n = 96) | Control (n = 95) | P value | |
Age, mean ± SD (range) | 56.7 ± 7.7a (29-80) | 54.01 ± 8.3b (27-66) | 40.54 ± 8.82c (22-61) | 33.37 ± 11d (19-62) | < 0.001 |
Gender | |||||
Male | 152a (79) | 67a (70) | 78a (81) | 21b (22) | < 0.001 |
Female | 40 a (21) | 29a (30) | 18a (19) | 74b (78) | |
Smoker | |||||
Yes | 75a (39) | 26ab (27) | 20b (21) | 3c (3) | < 0.001 |
No | 117a (61) | 70ab (73) | 76b (79) | 92c (97) | |
DM | |||||
Yes | 43a (22) | 22a (23) | 8b (8) | 0c (0) | < 0.001 |
No | 149a (78) | 74a (77) | 88b (92) | 95c (100) | |
HCV Ab | |||||
Present | 168a (88) | 90a (94) | 96b (100) | 0c | < 0.001 |
Absent | 24a (12) | 6a (6) | 0b (0) | 95c (100) | |
HBs Ag | |||||
Present | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0.57 |
Absent | 191 (100) | 96 (100) | 96 (100) | 95 (100) | |
Ascites | |||||
Yes | 86a (45) | 75b (78) | 0c (0) | 0c (0) | < 0.001 |
No | 106a (55) | 21b (22) | 96c (100) | 95c (100) | |
Child score | |||||
A | 69a (36) | 12b (12) | < 0.001 | ||
B | 69a (36) | 27a (28) | |||
C | 49a (28) | 57b (60) | |||
ALT, | |||||
mean | 64.79 ± 52.737 | 63.6 ± 42.54 | 63.41 ± 44.22 | 21.84 ± 5.04 | < 0.001 |
(range) | (5-395) | (6-290) | (10-223) | (11-33) | |
median | 51a | 60a | 54a | 22b | |
AST, | |||||
mean | 94.39 ± 105.61 | 53.91 ± 31.72 | 47.53 ± 29.04 | 26.68 ± 5.07 | < 0.001 |
(range) | (16-1155) | (16-176) | (8-167) | ( 15-37) | |
median | 77a | 46.5b | 39.5b | 27c | |
T-Bil, | |||||
mean | 2.4 ± 2.63 | 3.25 ± 2.51 | 0.88 ± 0.49 | 0.79 ± 0.16 | < 0.001 |
(range) | (0.3-25.8) | (0.2-19.7) | (0.3-5) | (0.5-1.1) | |
median | 1.7a | 2.86b | 0.84c | 0.8c | |
Albumin, | |||||
mean | 3.02 ± 0.63 | 2.55 ± 0.51 | 4.28 ± 0.4 | 4.45 ± 0.34 | < 0.001 |
(range) | (1.8-4.8) | (1.7-4.3) | (3.2-5.4) | (3.8-5.2) | |
median | 3.1a | 2.5b | 4.2c | 4.5d | |
AFP, | |||||
mean | 3933.25 ± 16142 | 35.21 ± 40.1 | 18.19 ± 29.62 | < 0.001 | |
(range) | (1.5-114170) | (1.7-190) | (0.65-112) | 0 | |
median | 152a | 17.95b | 4.6c | 0d |
Table 2 Levels of the studied serological markers in different investigated groups
HCC (n = 192) | Cirrhotic (n = 96) | Non-Cirrhotic (n = 96) | Control (n = 95) | P value | |
Proteosome, | |||||
median | 0.8a | 0.17b | 0.4c | 0.16d | < 0.001 |
mean ± SD | 0.91 ± 0.6 | 0.25 ± 0.25 | 0.68 ± 0.58 | 0.18 ± 0.3 | |
range | 0.13-1.87 | 0.12-1.67 | 0.09-1.83 | 0.01-2.22 | |
IL-8, | |||||
median | 107a | 55a | 36.5b | 47b | < 0.001 |
mean ± SD | 518.19 ± 656.23 | 552.9 ± 732.2 | 283.76 ± 442.7 | 238.8 ± 431.6 | |
range | 14-1837 | 14-1811 | 8-1734 | 3-1719 | |
sICAM-1, | |||||
median | 1072.5a | 892b | 510.5c | 473c | < 0.001 |
mean ± SD | 1034.73 ± 372.7 | 978.17 ± 540.17 | 570 ± 287 | 493 ± 188 | |
range | 79-2419 | 31-2838 | 46-1654 | 37-1078 | |
sTNF-RII, | |||||
median | 6785a | 7011.5b | 5948.5c | 3190.5d | < 0.001 |
mean ± SD | 7058.31 ± 1338.78 | 6984.5 ± 626.8 | 5456 ± 1531.7 | 3400 ± 1519 | |
range | 3250-12776 | 4351-9919 | 1772-9403 | 495-7157 | |
β-catenin, | |||||
median | 10.1a | 7.95b | 7.85b | 6.8c | < 0.001 |
mean ± SD | 11.26 ± 5.49 | 9.34 ± 5.13 | 8.81 ± 4.07 | 7.5 ± 3.2 | |
range | 4.3-55.4 | 5.0-49.2 | 3.8-41.6 | 4.3-28.4 |
Table 3 Correlation analysis of different studied markers showing Spearman’s rho value and P value
Proteosome | IL-8 | sICAM-1 | sTNF-RII | β-catenin | |
Proteosome | 1 | 0.2401 | 0.2401 | 0.1851 | 0.2301 |
0.000 | 0.000 | 0.000 | 0.000 | ||
IL-8 | 0.2401 | 1 | 0.2331 | 0.1841 | 0.1411 |
0.000 | 0.000 | 0.000 | 0.003 | ||
sICAM-1 | 0.2401 | 0.2331 | 1 | 0.5471 | 0.2221 |
0.000 | 0.000 | 0.000 | 0.000 | ||
sTNF-RII | 0.1851 | 0.1841 | 0.5471 | 1 | 0.2641 |
0.000 | 0.000 | 0.000 | 0.000 | ||
β-catenin | 0.2301 | 0.1411 | 0.2221 | 0.2641 | 1 |
0.000 | 0.003 | 0.000 | 0.000 |
Table 4 Area under curve of individual markers vs combined one using (method 1 and 2) in different combinations of groups
Method 1 | Method 2 | Proteasome | IL-8 | sICAM-1 | sTNF-RII | β-catenin | AFP | |
Disease vs Control | 0.979 | 0.992 | 0.834 | 0.612 | 0.825 | 0.951 | 0.768 | 0.923 |
HCC vs LC | 0.841 | 0.962 | 0.911 | 0.576 | 0.585 | 0.424 | 0.718 | 0.804 |
HCC vs HCV | 0.866 | 0.952 | 0.799 | 0.639 | 0.705 | 0.568 | 0.723 | 0.849 |
HCC vs Non-HCC | 0.917 | 0.970 | 0.848 | 0.652 | 0.787 | 0.724 | 0.771 | 0.902 |
HCV vs Control | 0.957 | 0.983 | 0.726 | 0.543 | 0.716 | 0.928 | 0.677 | 0.850 |
LC vs CHC | 0.695 | 0.951 | 0.220 | 0.648 | 0.769 | 0.829 | 0.494 | 0.736 |
CHC vs Control | 0.917 | 0.968 | 0.846 | 0.471 | 0.571 | 0.857 | 0.678 | 0.749 |
LC vs Control | 0.990 | 1.000 | 0.637 | 0.597 | 0.825 | 0.981 | 0.676 | 0.924 |
HCC vs Control | 0.998 | 1.000 | 0.927 | 0.672 | 0.917 | 0.970 | 0.846 | 0.986 |
HCC vs CHC | 0.967 | 0.971 | 0.648 | 0.724 | 0.867 | 0.762 | 0.730 | 0.908 |
Table 5 Statistical measurements of the diagnostic performance for the binary classifier over different pairwise comparison of the investigated groups
AUC | BT_Y | Spec (%) | Sen (%) | Acc (%) | TN | TP | FN | FP | NPV (%) | PPV (%) | |
Disease vs Control | 0.992 | 0.764 | 96.8 | 96.0 | 96.2 | 92 | 312 | 13 | 3 | 87.6 | 99.0 |
HCC vs LC | 0.962 | 0.655 | 98.8 | 89.1 | 92.3 | 85 | 156 | 19 | 1 | 81.7 | 99.3 |
HCC vs HCV | 0.952 | 0.712 | 98.7 | 80.5 | 88.9 | 148 | 141 | 34 | 2 | 81.3 | 98.6 |
HCC vs Others | 0.970 | 0.378 | 91.0 | 91.4 | 91.2 | 223 | 160 | 15 | 22 | 93.7 | 87.9 |
HCV vs Control | 0.983 | 0.764 | 96.8 | 91.3 | 93.5 | 92 | 137 | 13 | 3 | 87.6 | 97.8 |
LC vs CHC | 0.950 | 0.581 | 90.6 | 91.9 | 91.3 | 58 | 79 | 7 | 6 | 89.2 | 92.9 |
CHC vs Control | 0.968 | 0.341 | 90.5 | 93.7 | 91.8 | 86 | 60 | 4 | 9 | 95.5 | 86.9 |
LC vs Control | 1.000 | 0.500 | 100.0 | 100.0 | 100.0 | 95 | 86 | 0 | 0 | 100.0 | 100.0 |
HCC vs Control | 1.000 | 0.500 | 100.0 | 100.0 | 100.0 | 95 | 175 | 0 | 0 | 100.0 | 100.0 |
HCC vs CHC | 0.971 | 0.745 | 96.8 | 89.7 | 91.6 | 62 | 157 | 18 | 2 | 77.5 | 98.7 |
Table 6 Disease logistic predictive models based on binary-class classifier over different pairwise comparisons of the investigated groups
Combination | Model |
Disease vs Control | [-11 + 6.83 × Prot + (-5.99 × 10-5) × IL-8 + 3.12 × 10-4× sICAM + 0.0013 × sTNF-RII + 0.172aβ-catenin + 0.283 × AFP][P values = 6.83E-10, 1.86E-05, 0.938962, 0.764414, 6.79E-08, 0.225761, 0.000818] |
HCC vs LC | [11.33 + 7.380 × Prot + (-2.047 × 10-4) × IL-8 + 0.0011 × sICAM + 6.299 × 104× sTNF + 0.26 ×β-catenin + 0.016 × AFP][P values = 3.22E-05, 7.11E-07, 0.591834, 0.041838, 0.056595, 0.000357, 0.000638] |
HCC vs HCV | [-11.9 + 3.222 × Prot + (3.813 × 10-4) × IL + 0.00152 × sICAM + (6.481 × 10-4) × sTNF + 0.0291 ×β-catenin + 0.019 × AFP][P values = 1.39E-11, 2.63E-12, 0.231248, 0.000928, 0.000952, 5.41E-06, 5.09E-06] |
HCC vs Non-HCC | [-12.27 + 3.3 × Prot + 0.0004 × IL + 0.00155 × sICAM + (6.803 × 10-4) × sTNF + 0.294 ×β-catenin + 0.02 × AFP][P values = 5.26E-13, 4.14E-13, 0.211689, 0.000767, 0.000388, 3.89E-06, 3.42E-06] |
HCV vs Control | [-10.84 + 6.80 × Prot + (2.68 × 10-5) × IL-8 + 0.00017 × ICAM + 0.00126 × sTNF + 0.1742 ×β-catenin + 0.278 × AFP][P values = 1.12E-09, 1.87E-05, 0.972804, 0.875503, 9.02E-08, 0.227858, 0.000935] |
LC vs CHC | [-10.16 + (-4.487) × Prot + 0.00134 × IL-8 + 0.0021 × sICAM + 0.0018 × sTNF + (-0.2984) ×β-catenin + 0.0217 × AFP][P values = 0.002674, 0.000351, 0.052275., 0.021958, 0.000211, 0.009838, 0.030621] |
CHC vs Control | [-9.354 + 6.634 × Proteasome + (-0.00166) × IL-8 + (-0.00126) × sICAM + 0.001111 × sTNF + 0.208624 ×β-catenin + 0.24604 × AFP][P values = 1.40E-07, 1.64E-05, 0.2627, 0.3799, 8.55E-06, 0.1477, 0.0016] |
LC vs Control | [-515.7 + 108.7 × Proteasome + 0.01295 × IL-8 + 0.0194 × sICAM + 0.05745 × sTNF + 4.485 ×β-catenin + 12.59 × AFP][P values = 0.997, 0.998, 0.999, 0.999, 0.998, 0.998, 0.995] |
HCC vs Control | [-375.640 + 122.598 × Prot + (-0.0577) × IL + 0.0368 × sICAM + 0.0427 × sTNF + 1.1533 ×β-catenin + 13.584 × AFP][P values = 0.737, 0.802, 0.823, 0.917, 0.812, 0.923, 0.66] |
HCC vs CHC | [-10.40 + 1.416 × Prot + 0.002024 × IL-8 + 0.0041 × sICAM + (4.251 × 10-4) × sTNF + 0.2.67 ×β-catenin + 0.0244 × AFP][P values = 1.28E-07, 0.00826, 0.01827, 5.52E-05, 0.04942, 0.00391, 0.00354] |
Table 7 Final reduced disease logistic predictive models based on binary classifier with the most significant markers (achieved regression P < 0.05)
Final reduced model (with relevant terms) | Best threshold | |
Disease vs Control | (-11 + 6.83 × Prot + 0.00129 × sTNF + 0.283 × AFP) | 0.764 |
HCC vs LC | (-11.3 + 7.38 × Prot + 0.00108 × sICAM + 0.2574 ×β-catenin + 0.01597 × AFP) | 0.655 |
HCC vs HCV | [-11.91 + 3.222 × Prot + 0.001518 × sICAM + (6.481 × 10-4) × sTNF + 0.291 ×β-catenin + 0.0193 × AFP] | 0.712 |
HCC vs Non-HCC | [-12.27 + 3.299 × Prot + 0.001548 × sICAM + (6.803 × 10-4) × sTNF + 0.2936 ×β-catenin + 0.0198 × AFP] | 0.378 |
HCV vs Control | (-10.84 + 6.803 × Prot + 0.00126 × sTNF + 0.2783 × AFP) | 0.764 |
LC vs CHC | [-10.16 + (-4.487) × Prot + 0.002086 × sICAM + 0.001858 × sTNF + (-0.2984) ×β-catenin + 0.02169 × AFP] | 0.582 |
CHC vs Control | (-9.353476 + 6.63414 × Prot + 0.001111 × sTNF + 0.24604 × AFP) | 0.341 |
HCC vs CHC | [-10.40 + 1.416 × Prot + 0.002024 × IL-8 + 0.004096 × sICAM + (4.251 × 10-4) × sTNF + 0.2567 ×β-catenin + 0.02442 × AFP] | 0.745 |
- Citation: Zekri ARN, Youssef ASED, Bakr YM, Gabr RM, Ahmed OS, Elberry MH, Mayla AM, Abouelhoda M, Bahnassy AA. Early detection of hepatocellular carcinoma co-occurring with hepatitis C virus infection: A mathematical model. World J Gastroenterol 2016; 22(16): 4168-4182
- URL: https://www.wjgnet.com/1007-9327/full/v22/i16/4168.htm
- DOI: https://dx.doi.org/10.3748/wjg.v22.i16.4168