Correlation between clinical characteristic factors and baseline tumor markers
The median values of the baseline CA199, CEA and CA125were 1180 U/ml(range:0.60-20000 U/ml),7.23ug/L(range:0.21-5033ug/L),82.56 U/ml(range:5.10–4134 U/ml), respectively. The median CA199 level was significantly correlated with years of smoking(p = 0.024), diabetes(p = 0.012),year of diabetes(p = 0.012), tumor location(p = 0.007), number of organ metastases(p = 0.001), liver metastasis(p = 0.001).And the median level of CEA was significantly correlated with tumor location(p = 0.012), number of organ metastases(p = 0.008)and liver metastasis(p = 0.001). The medium CA125 level was significantly correlated with tumor location(p = 0.003), number of organ metastases(p = 0.042), liver metastasis = 0.028) (Table 1).
Table 1
Correlation between clinical characteristic factors and tumor markers
Features | CA199 | CEA | CA125 |
≤ 1180 >1180 Pb value | ≤ 7.23 >7.23 Pb value | ≤ 82.56 >82.56 Pb value |
Sex | | | 0.712 | | | 0.059 | | | 0.163 |
Male | 56 | 53 | | 61 | 48 | | 59 | 50 | |
Female | 83 | 86 | | 75 | 94 | | 77 | 92 | |
Age | | | 0.435 | | | 0.205 | | | 0.907 |
≤ 56 | 23 | 121 | | 70 | 74 | | 41 | 103 | |
༞56 | 17 | 117 | | 55 | 79 | | 39 | 95 | |
Smoke | | | 0.100 | | | 0.341 | | | 0.647 |
Yes | 53 | 53 | | 48 | 58 | | 50 | 56 | |
No | 86 | 86 | | 88 | 84 | | 86 | 86 | |
Year of smoking | | | 0.024 | | | 0.556 | | | 0.688 |
No smoking | 86 | 86 | | 87 | 85 | | 87 | 85 | |
1≤&≤10 | 2 | 11 | | 4 | 9 | | 5 | 8 | |
> 10 | 45 | 32 | | 38 | 39 | | 35 | 42 | |
Unknown | 6 | 10 | | 7 | 9 | | 9 | 7 | |
No. of cigarettes a | | | 0.171 | | | 0.264 | | | 0.500 |
0 | 86 | 86 | | 87 | 85 | | 87 | 85 | |
1≤&≤10 | 13 | 20 | | 11 | 22 | | 12 | 21 | |
> 10 | 37 | 26 | | 32 | 31 | | 32 | 31 | |
Unknown | 3 | 7 | | 6 | 4 | | 5 | 5 | |
Diabetes | | | 0.012 | | | 0.973 | | | 0.740 |
Yes | 20 | 37 | | 28 | 29 | | 29 | 28 | |
No | 119 | 102 | | 108 | 113 | | 107 | 114 | |
Year of diabetes | | | 0.012 | | | 0.124 | | | 0.456 |
No | 123 | 105 | | 111 | 117 | | 114 | 114 | |
≤ 1 | 7 | 7 | | 8 | 6 | | 8 | 6 | |
1<&≤10 | 4 | 16 | | 6 | 14 | | 9 | 11 | |
> 10 | 5 | 11 | | 11 | 5 | | 5 | 11 | |
Jaundice | | | 0.882 | | | 0.355 | | | 0.740 |
Yes | 28 | 29 | | 31 | 26 | | 29 | 28 | |
No | 111 | 110 | | 105 | 116 | | 107 | 114 | |
Tumor location | | | 0.007 | | | 0.012 | | | 0.003 |
Head | 64 | 42 | | 62 | 44 | | 64 | 42 | |
Body/tail | 75 | 97 | | 74 | 98 | | 72 | 100 | |
No. of metastasis | | | 0.001 | | | 0.008 | | | 0.042 |
0 | 32 | 16 | | 31 | 17 | | 31 | 17 | |
1 | 88 | 79 | | 83 | 84 | | 79 | 88 | |
≥ 2 | 19 | 44 | | 22 | 41 | | 26 | 37 | |
metastasis | | | | | | | | | |
Liver | | | 0.001 | | | 0.001 | | | 0.028 |
Yes | 95 | 119 | | 92 | 122 | | 97 | 117 | |
No | 44 | 20 | | 44 | 20 | | 39 | 25 | |
Lung | | | 0.157 | | | 0.211 | | | 0.340 |
Yes | 20 | 29 | | 20 | 29 | | 27 | 22 | |
No | 119 | 110 | | 116 | 113 | | 109 | 120 | |
a. Number of cigarettes (No smoking; ≤10 cigarettes/day; >10 cigarettes/day) |
b. Pearson chi-squared test(P < 0.05) |
Correlation between tumor markers and different parameters
After Pearson correlation analysis, it shows that baseline WBC related to baselineCA199(r = 0.296, p < 0.001), CEA (r = 0.249, p < 0.001), CA125(0.251, p < 0.001).Baseline LDH also correlated to baselineCA199(r = 0.299, p < 0.001), CEA (r = 0.178,P = 0.004), CA125(0.239, p < 0.001). Both CA199 and CA125 related to neutrophil (r = 0.313, P < 0.001; r = 0.223, p < 0.001, respectively). Otherwise, CA199 were related to baseline glycemic (r = 0.175, p = 0.004). In addition, baseline CA199 significantly related to CEA (r = 0.207, p = 0.001) and CA125(r = 0.402, p < 0.001) (Table 2, Fig. 1).
Table 2
Correlation between tumor markers and different peripheral blood parameters
Features | CA199 | | CEA | | CA125 |
Pearson pc Value correlation | Pearson p Value correlation | Pearson p Value correlation |
WBC | 0.296 | < 0.001 | | 0.249 | < 0.001 | | 0.251 | < 0.001 |
PLT | -0.087 | 0.149 | | 0.050 | 0.407 | | -0.054 | 0.378 |
Neutrophil | 0.313 | < 0.001 | | 0.079 | 0.196 | | 0.223 | < 0.001 |
ALB | -0.049 | 0.416 | | -0.033 | 0.587 | | -0.084 | 0.171 |
LDH | 0.299 | < 0.001 | | 0.178 | 0.004 | | 0.239 | < 0.001 |
TB | -0.017 | 0.784 | | -0.023 | 0.712 | | -0.042 | 0.491 |
Glycemic | 0.175 | 0.004 | | -0.014 | 0.823 | | -0.023 | 0.706 |
CEA | 0.207 | 0.001 | | 1 | | | 0.309 | < 0.001 |
CA199 | 1 | | | 0.207 | 0.001 | | 0.402 | < 0.001 |
CA125 | 0.402 | < 0.001 | | 0.309 | < 0.001 | | 1 | |
c Pearson’s correlation test. |
Univariate and multivariate analysis of prognostic factors
We used Cox proportional hazards regression model to identify the prognostic value of clinical characteristic factors and tumor markers. In the univariate analysis, the significant prognosis factors of patients were sex(p = 0.001), smoking(p = 0.020) year of smoking(p = 0.004), number of cigarettes (p = 0.030), baseline WBC (p = 0.022) baseline neutrophil (p < 0.001), LDH(p = 0.004), the median level of baseline CA199 (p = 0.006), the median level of CEA (p = 0.003), the median level of CA125(p < 0.001) (Table 3, Fig. 2).
Table 3
Univariate and multivariate analysis of prognostic factors
Features | N | mOS (month) | Univariate | Multivariate |
HR (95%CI) P value | HR (95%CI) P value |
Sex | | | | 0.001 | | |
Male | 109 | 12.1 | 1 | | | |
Female | 169 | 7.9 | 1.46(1.10–1.93) | | | |
Age | | | | 0.051 | | |
≤ 56 | 144 | 10.7 | 1 | | | |
༞56 | 134 | 9.0 | 1.31(1.00-1.71) | | | |
Smoke | | | | 0.020 | | |
No | 172 | 11.1 | 1 | | | |
Yes | 106 | 9.1 | 1.28(0.97–1.69) | | | |
Year of smoking | | | | 0.004 | | 0.025 |
No smoking | 172 | 11.1 | 1 | | 1 | |
1≤&≤10 | 13 | 7.9 | 2.64(1.41–4.94) | | 1.46(0.48–4.43) | |
> 10 | 77 | 9.9 | 1.11(0.82–1.51) | | 0.90(0.37–2.20) | |
Unknown | 16 | 5.9 | 1.78(1.02–3.10) | | 1.12(0.51–2.47) | |
No. of cigarettes | | | | 0.030 | | |
0 | 172 | 11.1 | 1 | | | |
1≤&≤10 | 33 | 6.0 | 1.85(1.22–2.80) | | | |
> 10 | 63 | 9.4 | 1.12(0.91–1.55) | | | |
Unknown | 10 | 9.2 | 1.14(0.55–2.33) | | | |
Diabetes | | | | 0.837 | | |
No | 221 | 9.9 | 1 | | | |
Yes | 57 | 9.2 | 0.90(0.65–1.25) | | | |
Year of diabetes | | | | 0.240 | | |
No | 228 | 9.9 | 1 | | | |
≤ 1 | 14 | 8.6 | 1.29(0.71–2.32) | | | |
1<&≤10 | 20 | 14.0 | 0.61(0.35–1.05) | | | |
> 10 | 16 | 6.0 | 1.03(0.56–1.89) | | | |
Jaundice | | | | 0.135 | | |
No | 221 | 10.6 | 1 | | | |
Yes | 57 | 7.5 | 1.11(0.80–1.52) | | | |
Tumor location | | | | 0.859 | | |
Head | 106 | 9.8 | 1 | | | |
Body/tail | 172 | 9.9 | 1.17(0.89–1.55) | | | |
No. of metastasis | | | | 0.162 | | |
0 | 48 | 12.7 | 1 | | | |
1 | 167 | 9.3 | 1.39(0.95–2.03) | | | |
≥ 2 | 63 | 10.9 | 1.32(0.85–2.04) | | | |
Metastasis | | | | | | |
Liver | | | | 0.077 | | |
No | 64 | 12.2 | 1 | | | |
Yes | 214 | 9.4 | 1.36(0.99–1.88) | | | |
Lung | | | | 0.632 | | |
No | 229 | 9.8 | 1 | | | |
Yes | 49 | 10.9 | 0.91(0.63–1.29) | | | |
First-line chemotherapy d | | | | 0.123 | | |
Gem | 40 | 6.2 | 1 | | | |
Gem-based | 43 | 11.0 | 0.70(0.44–1.22) | | | |
TG | 27 | 11.8 | 0.65(0.39–1.10) | | | |
TS | 159 | 9.9 | 0.63(0.44–0.91) | | | |
Others | 9 | 5.9 | 1.44(0.97–1.03) | | | |
TB | | | | 0.273 | | |
≤ULN | 239 | 10.3 | 1 | | | |
>ULN | 39 | 6.2 | 1.35(0.92–1.96) | | | |
Baseline glucose | | | | 0.969 | | |
≤ULN | 168 | 9.8 | 1 | | | |
>ULN | 110 | 9.9 | 0.95(0.73–1.26) | | | |
Baseline WBC | | | | 0.022 | | |
≤ULN | 248 | 10.4 | 1 | | | |
>ULN | 30 | 6.7 | 1.51(1.00-2.27) | | | |
Baseline PLT | | | | 0.233 | | |
≤ULN | 238 | 9.8 | 1 | | | |
>ULN | 40 | 12.1 | 0.82(0.55–1.22) | | | |
Baseline neutrophil | | | | < 0.001 | | 0.001 |
≤ULN | 187 | 11.2 | 1 | | 1.58(1.16–2.16) | |
>ULN | 91 | 7.0 | 2.02(1.52–2.67) | | | |
Baseline ALB | | | | 0.075 | | |
≤LLN | 30 | 5.8 | 1 | | | |
>LLN | 248 | 10.3 | 0.67(0.45–1.02) | | | |
Baseline LDH | | | | 0.004 | | |
≤ULN | 246 | 10.4 | 1 | | 1 | 0.017 |
>ULN | 32 | 6.5 | 1.87(1.26–2.78) | | 1.83(1.18–2.83) | |
Baseline CA199 | | | | < 0.001 | | 0.028 |
≤ 1180 | 139 | 12.2 | 1 | | 1 | |
> 1180 | 139 | 7.5 | 1.78(1.35–2.33) | | 1.47(1.08–2.01) | |
Baseline CEA | | | | 0.003 | | |
≤ 7.23 | 136 | 12.1 | 1 | | | |
> 7.23 | 142 | 7.9 | 1.50(1.14–1.96) | | | |
Baseline CA125 | | | | < 0.001 | | 0.001 |
≤ 82.56 | 136 | 12.7 | 1 | | 1 | |
> 82.56 | 142 | 7.4 | 2.13(1.61–2.81) | | 1.77(1.29–2.43) | |
c. Gem: Gemcitabine; Gem-based: Gemcitabine plus S1; Gemcitabine plus platinum;Gemcitabine plus capecitabine; TG: nab-paclitaxel plus gemcitabine; TS: nab-paclitaxel plus S1; Others: Oxaliplatin plus S1; Platinum monotherapy |
Multivariate analysis showed that year of smoking, normal level of baseline WBC, neutrophil counts, baseline LDH, the medium level of CA199,CEA, CA125were independent prognostic factors (HR = 1.51,P = 0.022; HR = 2.02, P < 0.001; HR = 1.87, P = 0.004; HR = 1.78, P < 0.001; HR = 1.50, P = 0.003; HR = 2.13, P < 0.001) (Table 3).
The elevation both the serum N, LDH, CA199 and CA125 associated with poor prognosis
Multivariate analysis showed that the baseline levels of N, LDH, CA199 and CA125 were independent prognosis factors in our research. Therefore, we combine the four markers to predict the relationship between the four markers and prognosis. And if the level of N,LDH exceeded the ULN or the level of CA199 and CA125 more than the medium level was defined as a score of 1.Finally,we divided the patients into 5 groups with scores of 0,1,2,3 and 4.The survival analysis showed that the patients with higher score had shorter OS with statistic significantly(P < 0.001)(Fig. 3).The medium OS of the patients with the score from 0 to 4 was 13.7, 14.0, 9.2, 5.7, 3.2 months, respectively. The result showed that the elevation both serum N, LDH, CA199 and CA125 associated with poor prognosis.