01.12.2017 | Research article | Ausgabe 1/2017 Open Access

A possible association of baseline serum IL-17A concentrations with progression-free survival of metastatic colorectal cancer patients treated with a bevacizumab-based regimen
- Zeitschrift:
- BMC Cancer > Ausgabe 1/2017
Background
Methods
Study design
Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
Multiplex
Survival analysis
Results
Demographic data and clinical features (Table 1)
Baseline patients’ characteristics (
n = 122)
|
||
---|---|---|
Age, years
|
65 [58–72]
|
|
Weight, kg
|
68 [60–77]
|
|
Height, cm (
n = 121)
|
170 [163–174]
|
|
Body surface area, m
2 (
n = 121)
|
1.75 [1.64–1.93]
|
|
Carcinoembryonic antigen, μg/L (
n = 111)
|
68.6 [11.8–271.3]]
|
|
Vascular endothelial growth factor, ng/L (
n = 119)
|
169.6 [61.9–334.5]
|
|
C
trough bevacizumab, mg/L
|
15.5 [11.7–22.8]
|
|
Time to progression, months
|
10.6 [7.4–16.1]
|
|
Follow-up period, months
|
23.9 [14.7–35.3]
|
|
Gender
|
male
|
77 (63%)
|
female
|
45 (37%)
|
|
World Health Organization Performance Status (
n = 116)
|
0
|
63 (52%)
|
1
|
51 (42%)
|
|
2
|
2 (2%)
|
|
Primary tumor site
|
Colon
|
85 (70%)
|
Rectal
|
37 (30%)
|
|
Combined chemotherapy
|
FOLFIRI
|
81 (66%)
|
FOLFOX
|
21 (17%)
|
|
LV5FU2
|
8 (7%)
|
|
Others
|
12 (10%)
|
Polymorphisms
Polymorphisms
|
n
|
(%)
|
---|---|---|
IL-17A (rs2275913)
|
||
AA
|
14
|
11,47
|
AG
|
63
|
51,65
|
GG
|
45
|
36,88
|
IL-17F (rs763780)
|
||
AA
|
116
|
95,08
|
AG
|
6
|
4,92
|
GG
|
0
|
0
|
Cytokine concentrations
Cytokine
|
Median concentration (pg/ml)
|
Range
|
---|---|---|
IL-1β
|
0.24
|
[0.24–2.52]
|
IL-4
|
1.33
|
[1.33–95.56]
|
IL-6
|
13.08
|
[1.65–684.30]
|
IL-10
|
1.99
|
[1.99–70.69]
|
IL-17A
|
1.20
|
[1.20–83.17]
|
IL-17F
|
3.04
|
[3.04–128.41]
|
IL-21
|
8.97
|
[8.97]
|
IL-22
|
3.88
|
[3.88–21.09]
|
IL-23
|
7.35
|
[7.35–133.54]
|
IL-25
|
1.00
|
[1.00–1.63]
|
IL-31
|
3.87
|
[3.87–1089.37]
|
IL-33
|
4.18
|
[4.18–391.39]
|
IFNγ
|
2.54
|
[2.54]
|
sCD40L
|
493.64
|
[2.41–4580.84]
|
TNFα
|
0.75
|
[0.57–11.32]
|
Overall survival (Table 4)
HR
|
95% CI
|
p
|
|
---|---|---|---|
Univariate analysis: Covariate
|
|||
Gender (female)
|
0.68
|
0.44–1.06
|
0.092
|
Age, years
|
1.01
|
0.99–1.03
|
0.55
|
Vascular endothelial growth factor, μg/L
|
2.09
|
1.10–3.99
|
0.025
|
C
trough bevacizumab <15.5 mg/L
|
2.34
|
1.52–3.58
|
9.9 × 10
−5
|
Log(carcinoembryonic antigen), μg/L
|
1.21
|
1.10–1.34
|
9.8 × 10
−5
|
IL17A polymorphism (A carriers)
|
0.86
|
0.56–1.30
|
0.47
|
IL17F polymorphism (AG)
|
1.80
|
0.87–3.73
|
0.11
|
IL-1β, pg/mL
|
1.23
|
0.69–2.21
|
0.48
|
IL-4, pg/mL
|
1.00
|
0.99–1.01
|
0.96
|
IL-6, pg/mL
|
1.00
|
0.99–1.00
|
0.49
|
IL-10, pg/mL
|
1.00
|
0.99–1.02
|
0.61
|
IL-17A, pg/mL
|
1.01
|
0.99–1.03
|
0.22
|
IL-17F, pg/mL
|
0.99
|
0.97–1.01
|
0.34
|
IL-22, pg/mL
|
1.07
|
0.99–1.15
|
0.057
|
IL-31, pg/mL
|
1.00
|
1.00–1.004
|
0.019
|
IL-33, pg/mL
|
1.00
|
0.99–1.00
|
0.95
|
sCD40L, pg/mL
|
1.00
|
0.86–1.06
|
0.83
|
Tumor necrosis factorα, pg/mL
|
0.97
|
0.86–1.09
|
0.61
|
Multivariate analysis: Covariate
|
|||
C
trough bevacizumab <15.5 mg/L
|
1.88
|
1.19–2.97
|
0.0064
|
Log(CEA), μg/L
|
1.15
|
1.04–1.28
|
0.0057
|
Progression-free survival (Table 5)
HR
|
95% CI
|
p
|
|
---|---|---|---|
Univariate analysis: Covariate
|
|||
Gender (female)
|
0.70
|
0.47–1.03
|
0.07
|
Age, years
|
1.01
|
0.99–1.02
|
0.52
|
Vascular endothelial growth factor, μg/L
|
2.54
|
1.44–4.48
|
0.0013
|
C
trough bevacizumab <15.5 mg/L
|
1.88
|
1.28–2.74
|
0.0011
|
Log(carcinoembryonic antigen), μg/L
|
1.10
|
1.02–1.19
|
0.017
|
IL-17A polymorphism (A carriers)
|
0.80
|
0.55–1.17
|
0.26
|
IL-17F polymorphism (AG)
|
1.27
|
0.64–2.52
|
0.49
|
IL-1β, pg/mL
|
1.34
|
0.77–2.33
|
0.31
|
IL-4, pg/mL
|
1.00
|
0.99–1.01
|
0.74
|
IL-6, pg/mL
|
1.00
|
0.59–0.55
|
0.55
|
IL-10, pg/mL
|
1.01
|
0.99–1.02
|
0.49
|
IL-17A, pg/mL
|
1.02
|
1.00–1.04
|
0.026
|
IL-17F, pg/mL
|
1.00
|
0.99–1.02
|
0.65
|
IL-22, pg/mL
|
1.03
|
0.95–1.10
|
0.49
|
IL-31, pg/mL
|
1.00
|
0.99–1.00
|
0.089
|
IL-33, pg/mL
|
1.00
|
0.99–1.00
|
0.13
|
sCD40L, pg/mL
|
1.00
|
0.99–1.00
|
0.8
|
Tumor necrosis factorα, pg/mL
|
1.10
|
0.99–1.21
|
0.067
|
Multivariate analysis: Covariate
|
|||
Vascular endothelial growth factor, μg/L
|
2.34
|
1.31–4.20
|
0.0041
|
C
trough bevacizumab <15.5 mg/L
|
1.72
|
1.17–2.53
|
0.0059
|
IL-17A, pg/mL
|
1.02
|
1.001–1.04
|
0.043
|