Case Control Study
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
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
Male152a (79)67a (70)78a (81)21b (22)< 0.001
Female40 a (21)29a (30)18a (19)74b (78)
Smoker
Yes75a (39)26ab (27)20b (21)3c (3)< 0.001
No117a (61)70ab (73)76b (79)92c (97)
DM
Yes43a (22)22a (23)8b (8)0c (0)< 0.001
No149a (78)74a (77)88b (92)95c (100)
HCV Ab
Present168a (88)90a (94)96b (100)0c< 0.001
Absent24a (12)6a (6)0b (0)95c (100)
HBs Ag
Present0 (0)0 (0)0 (0)0 (0)0.57
Absent191 (100)96 (100)96 (100)95 (100)
Ascites
Yes86a (45)75b (78)0c (0)0c (0)< 0.001
No106a (55)21b (22)96c (100)95c (100)
Child score
A69a (36)12b (12)< 0.001
B69a (36)27a (28)
C49a (28)57b (60)
ALT,
mean64.79 ± 52.73763.6 ± 42.5463.41 ± 44.2221.84 ± 5.04< 0.001
(range)(5-395)(6-290)(10-223)(11-33)
median51a60a54a22b
AST,
mean94.39 ± 105.6153.91 ± 31.7247.53 ± 29.0426.68 ± 5.07< 0.001
(range)(16-1155)(16-176)(8-167)( 15-37)
median77a46.5b39.5b27c
T-Bil,
mean2.4 ± 2.633.25 ± 2.510.88 ± 0.490.79 ± 0.16< 0.001
(range)(0.3-25.8)(0.2-19.7)(0.3-5)(0.5-1.1)
median1.7a2.86b0.84c0.8c
Albumin,
mean3.02 ± 0.632.55 ± 0.514.28 ± 0.44.45 ± 0.34< 0.001
(range)(1.8-4.8)(1.7-4.3)(3.2-5.4)(3.8-5.2)
median3.1a2.5b4.2c4.5d
AFP,
mean3933.25 ± 1614235.21 ± 40.118.19 ± 29.62< 0.001
(range)(1.5-114170)(1.7-190)(0.65-112)0
median152a17.95b4.6c0d
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,
median0.8a0.17b0.4c0.16d< 0.001
mean ± SD0.91 ± 0.60.25 ± 0.250.68 ± 0.580.18 ± 0.3
range0.13-1.870.12-1.670.09-1.830.01-2.22
IL-8,
median107a55a36.5b47b< 0.001
mean ± SD518.19 ± 656.23552.9 ± 732.2283.76 ± 442.7238.8 ± 431.6
range14-183714-18118-17343-1719
sICAM-1,
median1072.5a892b510.5c473c< 0.001
mean ± SD1034.73 ± 372.7978.17 ± 540.17570 ± 287493 ± 188
range79-241931-283846-165437-1078
sTNF-RII,
median6785a7011.5b5948.5c3190.5d< 0.001
mean ± SD7058.31 ± 1338.786984.5 ± 626.85456 ± 1531.73400 ± 1519
range3250-127764351-99191772-9403495-7157
β-catenin,
median10.1a7.95b7.85b6.8c< 0.001
mean ± SD11.26 ± 5.499.34 ± 5.138.81 ± 4.077.5 ± 3.2
range4.3-55.45.0-49.23.8-41.64.3-28.4
Table 3 Correlation analysis of different studied markers showing Spearman’s rho value and P value
ProteosomeIL-8sICAM-1sTNF-RIIβ-catenin
Proteosome10.24010.24010.18510.2301
0.0000.0000.0000.000
IL-80.240110.23310.18410.1411
0.0000.0000.0000.003
sICAM-10.24010.233110.54710.2221
0.0000.0000.0000.000
sTNF-RII0.18510.18410.547110.2641
0.0000.0000.0000.000
β-catenin0.23010.14110.22210.26411
0.0000.0030.0000.000
Table 4 Area under curve of individual markers vs combined one using (method 1 and 2) in different combinations of groups
Method 1Method 2ProteasomeIL-8sICAM-1sTNF-RIIβ-cateninAFP
Disease vs Control0.9790.9920.8340.6120.8250.9510.7680.923
HCC vs LC0.8410.9620.9110.5760.5850.4240.7180.804
HCC vs HCV0.8660.9520.7990.6390.7050.5680.7230.849
HCC vs Non-HCC0.9170.9700.8480.6520.7870.7240.7710.902
HCV vs Control0.9570.9830.7260.5430.7160.9280.6770.850
LC vs CHC0.6950.9510.2200.6480.7690.8290.4940.736
CHC vs Control0.9170.9680.8460.4710.5710.8570.6780.749
LC vs Control0.9901.0000.6370.5970.8250.9810.6760.924
HCC vs Control0.9981.0000.9270.6720.9170.9700.8460.986
HCC vs CHC0.9670.9710.6480.7240.8670.7620.7300.908
Table 5 Statistical measurements of the diagnostic performance for the binary classifier over different pairwise comparison of the investigated groups
AUCBT_YSpec (%)Sen (%)Acc (%)TNTPFNFPNPV (%)PPV (%)
Disease vs Control0.9920.76496.896.096.29231213387.699.0
HCC vs LC0.9620.65598.889.192.38515619181.799.3
HCC vs HCV0.9520.71298.780.588.914814134281.398.6
HCC vs Others0.9700.37891.091.491.2223160152293.787.9
HCV vs Control0.9830.76496.891.393.59213713387.697.8
LC vs CHC0.9500.58190.691.991.358797689.292.9
CHC vs Control0.9680.34190.593.791.886604995.586.9
LC vs Control1.0000.500100.0100.0100.0958600100.0100.0
HCC vs Control1.0000.500100.0100.0100.09517500100.0100.0
HCC vs CHC0.9710.74596.889.791.66215718277.598.7
Table 6 Disease logistic predictive models based on binary-class classifier over different pairwise comparisons of the investigated groups
CombinationModel
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