Background
Methods
Study subjects and sample collection
Measurement of serum cytokine levels using a chemiluminescent immunoassay
Measurement of serum levels of CA19-9 and CEA
Statistical analysis
Results
Serum sCD40L levels along the PDAC carcinogenic sequence in training set: comparison with serum CA19-9 and CEA
(Training set) | Groups (n) | |||
---|---|---|---|---|
Values | Normal (n = 25) | CP†(n = 25) | PDAC (n = 25) |
p- value‡
|
Serum sCD40L (ng/ml) | 9170.5 ± 5449.8* | 17648.9 ± 7264.0 | 30044.2 ± 9747.9 | < 0.001 |
Serum CA19-9 (U/ml) | 7.9 ± 7.1 | 136.8 ± 329.8 | 5795.4 ± 7842.7 | < 0.001 |
Serum CEA (ng/ml) | 2.3 ± 1.5 | 2.9 ± 2.0 | 367.9 ± 1709.4 | 0.428 |
(Validation set)
|
Groups (n)
| |||
Values
|
Normal (n = 30)
|
CP (n = 30)
|
PDAC (n = 55)
|
p-
value
‡
|
Serum sCD40L (ng/ml) | 10540.1 ± 5159.9 | 18709.4 ± 8786.6 | 27924.6 ± 10202.9 | < 0.001 |
Serum CA19-9 (U/ml) | 8.5 ± 7.5 | 119.6 ± 299.7 | 3932.7 ± 6839.2 | < 0.001 |
Serum CEA (ng/ml) | 2.2 ± 1.4 | 2.6 ± 2.0 | 271.4 ± 1246.8 | 0.359 |
Diagnostic accuracy of sCD40L for PDAC prediction in training set
Serum sCD40L levels along the PDAC carcinogenic sequence in independent validation dataset
Diagnostic potential of sCD40L for predicting PDAC in the validation dataset
Marker panel* | Cut-off point†
| Sensitivity‡
| Specificity |
---|---|---|---|
sCD40L | 0.45 | 80.0% | 85.5% |
CA19-9 | 0.35 | 80.0% | 72.7% |
CEA | 0.45 | 68.9% | 60.0% |
sCD40L + CA19-9 | 0.35 | 80.0% | 89.1% |
sCD40L + CEA | 0.60 | 80.0% | 85.5% |
CA19-9 + CEA | 0.41 | 80.0% | 70.9% |
sCD40L + CA19-9 + CEA | 0.45 | 84.4% | 90.9% |
Correlations between serum sCD40L and clinicopathological characteristics of PDAC
sCD40L | CA19-9 | |
---|---|---|
γs(p- value) | γs(p- value) | |
Gender (Male: Female) | -0.046 (0.740) | -0.213 (0.126) |
Age (≤40, > 40 & ≤60, > 60) | 0.076 (0.581) | -0.181 (0.194) |
T-stage (T1, T2, T3 ,T4) | 0.194 (0.156) | 0.095 (0.501) |
Node metastasis (N0, N1) | -0.146 (0.289) |
0.362 (0.008)
|
Distant metastasis (M0, M1) |
0.294(0.030)
|
0.425 (0.002)
|
Overall stage (I, II, III, IV) |
0.319 (0.017)
|
0.431 (0.001)
|
Size (≤2 cm, > 2 cm & ≤5 cm, > 5 cm) | 0.035 (0.801) | 0.179 (0.201) |
Unresectability* |
0.342 (0.011)
| 0.269 (0.051) |
Correlations between serum sCD40L and pro-angiogenic or immunosuppressive cytokines in patients with PDAC in the validation dataset
(All groups) | EGF | VEGF | IL-8 | IL-6 | IL-10 | IL-1RA | |
---|---|---|---|---|---|---|---|
Serum sCD40L
|
(γ
p
)
| 0.590 | 0.389 | 0.195 | 0.203 | 0.215 | 0.243 |
(p- value) |
< 0.001
|
< 0.001
|
0.037
|
0.029
|
0.021
|
0.009
| |
(PDAC group)
|
EGF
|
VEGF
|
IL-8
|
IL-6
|
IL-10
|
IL-1RA
| |
Serum sCD40L
|
(γ
p
)
| 0.397 | 0.305 | 0.257 | 0.209 | 0.224 | 0.248 |
(p- value) |
0.003
|
0.026
| 0.058 | 0.126 | 0.100 | 0.068 |
Diagnostic advantage of serum sCD40L to overcome the limitations of CA19-9
Low-serum CA 19–9 subjects | High-serum CA 19–9 subjects | |||||
---|---|---|---|---|---|---|
Cut-off value | Sensitivity | Specificity | Cut-off value | Sensitivity | Specificity | |
sCD40L (ng/ml)
| 20000 | 80.0% | 86.7% | 20000 | 77.0% | 85.0% |
Prediction of PDAC prognosis by serum sCD40L levels
Univariate analysis | HRs | 95% CI |
p -value |
---|---|---|---|
Gender (male vs. female) | 0.583 | 0.280-1.211 | 0.148 |
Age (≤40, > 40 & ≤60, > 60) | 0.649 | 0.359-1.175 | 0.154 |
T-stage (T1, T2, T3 ,T4) | 1.428 | 0.902-2.261 | 0.129 |
Node metastasis (N0, N1) | 1.960 | 0.810-4.745 | 0.136 |
Distant metastasis (M0, M1) | 3.558 | 1.695-7.469 | 0.001 |
Unresectability (resectable vs. unresectable) | 2.917 | 1.025-8.298 | 0.045 |
Tumor Size (≤2 cm, > 2 cm & ≤ 5 cm, > 5 cm) | 2.419 | 1.191-4.917 | 0.015 |
Histological differentiation (Well, Moderate, Poor; n) | 1.154 | 0.777-1.714 | 0.478 |
Karnofsky performance status scale (continuous variable)* | 0.962 | 0.936-0.988 | 0.005 |
High-serum CA19-9 (≤40 U/ml vs. > 40 U/ml) | 1.811 | 0.788-4.160 | 0.162 |
High-serum CEA (≤3 ng/ml vs. > 3 ng/ml) | 2.137 | 1.062-4.298 | 0.033 |
High-serum sCD40L (≤35,000 ng/ml vs. > 35,000 ng/ml) | 2.468 | 1.162-5.242 | 0.019 |
Multivariate analysis
|
HRs
†
|
95% CI
|
p
-value
|
Distant metastasis (M0, M1) | 3.469 | 1.375-8.749 | 0.008 |
Unresectability (resectable vs. unresectable) | 0.588 | 0.168-2.060 | 0.406 |
Tumor Size (≤2 cm, > 2 cm & ≤ 5 cm, > 5 cm) | 2.454 | 1.075-5.602 | 0.033 |
Karnofsky performance status scale (continuous variable)* | 0.969 | 0.940-0.998 | 0.038 |
High-serum CEA (≤3 ng/ml vs. > 3 ng/ml) | 1.354 | 0.549-3.340 | 0.511 |
High-serum sCD40L (≤35,000 ng/ml vs. > 35,000 ng/ml) | 2.509 | 1.038-6.067 | 0.041 |