Demographic characteristics and the prognostic efficacy of ACR
As shown in Fig. 1, a total of 294 patients were registered, and 156 patients (100 males, 56 females) were ultimately included in the study. The mean age of the patients was 60.36 y (range: 24–85 y), and the mean follow-up was 47.61 m (range: 1–102 m). According to the ROC tests, ACR was significant for predicting PFS (AUC = 0.75, 95% CI: 0.368–0.83, P < 0.01) and OS (AUC = 0.74, 95% CI: 0.65–0.83, P < 0.01) (Fig. 2), and when 5.98 (according to the Youden index) was used as the cutoff point, it had a sensitivity of 58.50% and 61.50% and a specificity of 83.50% and 80.50% for PFS and OS, respectively. Next, further comparison of the prognostic efficacy of ACR with other markers indicated that ACR had a superior efficacy than individual ALB (Z = 2.58, P = 0.01), CEA (Z = 2.17, P = 0.03) and NLR (Z = 2.63, P = 0.01), LMR (Z = 2.08, P = 0.01), PLR (Z = 3.03, P<0.01) in PFS; and it also had a similar advantage over single ALB (Z = 2.05, P = 0.04), CEA (Z = 2.04, P = 0.04) and NLR (Z = 2.29, P = 0.02), PLR (Z = 2.40, P = 0.02) in OS except LMR (Z = 1.72, P = 0.09).
Differences in clinicopathological parameters in the ACR-low or ACR-high subgroups
By ROC tests, the patients were subsequently divided into ACR-low (< 5.98) or ACR-high (≥ 5.98) subgroups, and it was found that 31.41% (49/156) of cases were ACR-low.
As shown in Table 1, these patients apparently presented with advanced T stages (T3 + T4) (P<0.01), larger tumor diameters (P<0.01) and distant metastases (P = 0.01) and a relatively lower LMR (P<0.01).
Table 1
Different ACR among varied clinicopathological parameters
|
|
ACR
|
|
Patient No.
|
<5.98
|
≥ 5.98
|
P
|
Age (y)
|
|
|
|
0.08
|
< 60
|
68
|
16
|
52
|
|
≥ 60
|
88
|
33
|
55
|
|
Gender
|
|
|
|
0.47
|
Female
|
56
|
20
|
36
|
|
Male
|
100
|
29
|
71
|
|
Tumor location
|
|
|
|
1.00
|
Right
|
36
|
11
|
25
|
|
Left
|
110
|
38
|
82
|
|
Histological grade
|
|
|
|
0.12
|
Well + moderate
|
127
|
36
|
91
|
|
Poor
|
29
|
13
|
16
|
|
Invasive depth
|
|
|
|
<0.01*
|
T1 + 2
|
34
|
4
|
30
|
|
T3 + 4
|
122
|
45
|
77
|
|
Tumor diameter (cm)
|
|
|
|
<0.01*
|
<4
|
64
|
12
|
52
|
|
≥4
|
92
|
37
|
55
|
|
Node involvement
|
|
|
|
0.23
|
N0
|
91
|
25
|
66
|
|
N1 + 2
|
65
|
24
|
41
|
|
Positive nodes no.
|
156
|
3.12 ± 5.78
|
1.64 ± 3.88
|
0.15
|
Distant metastasis
|
|
|
|
0.01*
|
Yes
|
12
|
8
|
4
|
|
No
|
144
|
41
|
103
|
|
TNM stage
|
|
|
|
0.17
|
I + II
|
87
|
23
|
64
|
|
III + IV
|
69
|
26
|
43
|
|
Adjuvant therapies
|
|
|
|
0.02
|
Received
|
85
|
31
|
54
|
|
None
|
52
|
9
|
43
|
|
Unknown
|
19
|
9
|
10
|
|
BMI (kg/m2)
|
156
|
23.22 ± 4.78
|
23.89 ± 3.23
|
0.11
|
Preoperative measures
|
|
|
|
|
NLR
|
156
|
3.18 ± 2.88
|
2.52 ± 2.75
|
0.17
|
LMR
|
156
|
3.43 ± 1.61
|
4.20 ± 1.69
|
<0.01*
|
PLR
|
156
|
165.91 ± 94.37
|
148.24 ± 87.25
|
0.25
|
*with significant statistical difference; no. number. |
Survival differences of ACR-low or ACR-high groups in PFS and OS
There were significant differences in the ACR-low or ACR-high subgroups in the 3-year PFS (63.27% vs. 20.56%, P<0.01) and OS (48.98% vs. 14.02%, P<0.01) rates. By K-M analyses, it was found that patients with ACR-low had a significantly worse PFS (ACR-low vs. high: 29.35 ± 24.73 m vs. 49.81 ± 21.43 m, Log Rank = 35.75, P<0.01) and OS (ACR-low vs. high: 35.22 ± 21.94 m vs. 53.28 ± 18.98 m, Log Rank = 29.68, P<0.01) than those with ACR-high (Fig. 3).
Univariate and multivariate analyses of the prognostic factors for PFS and OS
Univariate tests indicated that invasive depth, tumor diameter, node involvement, positive node number, distant metastasis, TNM stage, NLR, LMR and ACR were significant prognostic factors for PFS and OS (additional plus age and histological grade) (Table 2), and when all these factors were included in multivariate tests, the results indicated that the ACR was an independent prognostic factor for both PFS (HR = 0.31, 95% CI: 0.17–0.56, P<0.01) and OS (HR = 0.33, 95% CI: 0.16–0.66, P<0.01) (Table 3).
Table 2
Univariate and multivariate analyses of different parameters for PFS
|
Univariate
|
Multivariate
|
|
P
|
HR
|
95%CI
|
P
|
HR
|
95%CI
|
Age (years)
|
|
|
|
|
|
|
<60
|
1
|
|
|
|
|
|
≥60
|
0.16
|
1.51
|
0.85–2.67
|
|
|
|
Gender
|
|
|
|
|
|
|
Female
|
1
|
|
|
|
|
|
Male
|
0.32
|
1.35
|
0.75–2.43
|
|
|
|
Tumor location
|
|
|
|
|
|
|
Right
|
|
|
|
|
|
|
Left
|
0.26
|
1.51
|
0.74–3.10
|
|
|
|
Histological grade
|
|
|
|
|
|
|
Well + moderate
|
1
|
|
|
|
|
|
Poor
|
0.15
|
1.61
|
0.84–3.06
|
|
|
|
Invasive depth
|
|
|
|
|
|
|
T1 + 2
|
1
|
|
|
1
|
|
|
T3 + 4
|
< 0.01*
|
5.81
|
1.81–18.67
|
0.04*
|
3.34
|
1.02–11.01
|
Tumor diameter (cm)
|
|
|
|
|
|
|
<4
|
1
|
|
|
|
|
|
≥4
|
0.13
|
1.56
|
0.88–2.79
|
|
|
|
Node involvement
|
|
|
|
|
|
|
N0
|
1
|
|
|
|
|
|
N1 + 2
|
0.03*
|
1.86
|
1.08–3.21
|
|
|
|
Positive nodes no.
|
< 0.01*
|
1.11
|
1.06–1.16
|
0.03*
|
1.05
|
1.01–1.10
|
Distant metastasis
|
|
|
|
|
|
|
Yes
|
1
|
|
|
|
|
|
No
|
< 0.01*
|
7.89
|
3.88–16.02
|
< 0.01*
|
3.04
|
1.40–6.61
|
TNM stage
|
|
|
|
|
|
|
I + II
|
1
|
|
|
|
|
|
II + IV
|
< 0.01*
|
2.19
|
1.26–3.80
|
|
|
|
Adjuvant therapies
|
|
|
|
|
|
|
Received
|
1
|
|
|
|
|
|
None + Unknow
|
0.07
|
1.69
|
0.96-3.00
|
|
|
|
BMI (kg/m2)
|
0.39
|
0.97
|
0.89–1.05
|
|
|
|
Preoperative measures
|
NLR
|
< 0.01*
|
1.09
|
1.03–1.15
|
< 0.01*
|
1.09
|
1.03–1.16
|
LMR
|
< 0.01*
|
0.77
|
0.64–0.93
|
|
|
|
PLR
|
0.17
|
1.00
|
1.00–1.00
|
|
|
|
ACR
|
|
|
|
|
|
|
<5.98
|
1
|
|
|
|
|
|
≥5.98
|
< 0.01*
|
0.21
|
0.12–0.37
|
< 0.01*
|
0.31
|
0.17–0.56
|
*with significant statistical difference |
Table 3. Univariate and multivariate analyses of different parameters for PFS
|
Univariate
|
Multivariate
|
|
P
|
HR
|
95%CI
|
P
|
HR
|
95%CI
|
Age (years)
|
|
|
|
|
|
|
<60
|
1
|
|
|
|
|
|
≥60
|
0.02*
|
2.28
|
1.13-4.59
|
|
|
|
Gender
|
|
|
|
|
|
|
Female
|
1
|
|
|
|
|
|
Male
|
0.45
|
1.30
|
0.66-2.57
|
|
|
|
Tumor location
|
|
|
|
|
|
|
Right
|
|
|
|
|
|
|
Left
|
0.37
|
1.45
|
0.64-3.29
|
|
|
|
Histological grade
|
|
|
|
|
|
|
Well+moderate
|
1
|
|
|
|
|
|
Poor
|
0.04*
|
2.02
|
1.01-4.06
|
|
|
|
Invasive depth
|
|
|
|
|
|
|
T1+2
|
1
|
|
|
|
|
|
T3+4
|
0.01*
|
13.49
|
1.85-98.31
|
|
|
|
Tumor diameter (cm)
|
0.02*
|
1.16
|
1.03-1.30
|
|
|
|
<4
|
1
|
|
|
|
|
|
≥4
|
0.03
|
2.19
|
1.07-4.50
|
|
|
|
Node involvement
|
|
|
|
|
|
|
N0
|
1
|
|
|
|
|
|
N1+2
|
0.01*
|
2.21
|
1.17-4.17
|
|
|
|
Positive nodes no.
|
<0.01*
|
1.14
|
1.09-1.20
|
<0.01*
|
1.08
|
1.02-1.13
|
Distant metastasis
|
|
|
|
|
|
|
Yes
|
1
|
|
|
1
|
|
|
No
|
<0.01*
|
8.71
|
4.01-18.94
|
<0.01*
|
4.41
|
1.92-10.10
|
TNM stage
|
|
|
|
|
|
|
I+II
|
1
|
|
|
|
|
|
II+IV
|
<0.01*
|
2.57
|
1.34-4.89
|
|
|
|
Adjuvant therapies
|
|
|
|
|
|
|
Received
|
1
|
|
|
|
|
|
None+Unknow
|
0.43
|
1.30
|
0.68-2.48
|
|
|
|
BMI (kg/m2)
|
0.40
|
0.96
|
0.88-1.05
|
|
|
|
Preoperative measures
|
NLR
|
<0.01*
|
1.10
|
1.04-1.17
|
<0.01*
|
1.10
|
1.03-1.18
|
LMR
|
0.03*
|
0.79
|
0.63-0.98
|
|
|
|
PLR
|
0.23
|
1.00
|
1.00-1.01
|
|
|
|
ACR
|
|
|
|
|
|
|
<5.98
|
1
|
|
|
|
|
|
≥5.98
|
<0.01*
|
0.20
|
0.10-0.38
|
<0.01*
|
0.33
|
0.16-0.66
|
*with significant statistical difference