The serum level of gastrin-17, CEA, CA12-5 and CA19-9 in gastric cancer and control groups
Totally, 329 participants (230 GC patients and 99 healthy controls) were included in this study. There was no statistical significance between the two groups in terms of age, gender and body height (P > 0.05). However, the body weight and BMI were much higher in healthy control group than in the GC group (P < 0.05), which might be caused by the disease of GC (Table 1).
Table 1
The clinical characteristics of participants in gastric cancer and control groups
| | GC group (n = 230) | Control group (n = 99) | P value |
Age (years) | | 57.0 (48.0–66.0) | 54.0 (44.0–63.0) | 0.153 |
Gender (M/F) | | 152/78 | 56/43 | 0.100 |
Height (cm) | | 162.0 (156.0-168.0) | 165.0 (158.0-170.0.) | 0.064 |
BW (kg) | | 55.3 (50.0–62.0) | 63.5 (55.0–72.0) | < 0.001 |
BMI (kg/m2) | | 20.9 (19.3–23.6) | 23.8 (21.4–25.8) | < 0.001 |
BW: body weight, BMI: body mass index, GC: gastric cancer, M: male, F: female |
According to the test results, the median level of Gastrin-17, CEA, CA199 and CA125 were 4.55 pmol/L, 2.22 ng/mL, 10.00 Uarb/mL and 11.55 Uarb/mL in GC group, respectively. And the median level of Gastrin-17, CEA, CA199 and CA125 were 1.95 pmol/L, 1.76 ng/mL, 4.51 Uarb/mL and 9.40 Uarb/mL in healthy control group, respectively, which were all much lower than that in GC group (P < 0.05, Table 2). According to the normal reference range of Gastrin-17, CEA, CA199 and CA125 in our institution, the positive rate of Gastrin-17, CEA, CA199 and CA125 were 22.61%, 22.61%, 20.00% and 8.26% in GC group, respectively; and were 5.05%, 2.02%, 1.01% and 2.02% in healthy control group, respectively, suggesting much lower positive rates in healthy control group (P < 0.05, Table 2).
Table 2
The level and positive rate of serum markers in gastric cancer and control groups
| GC group | Control group | P value |
Serum level | Positive N (%) | Serum level | Positive N (%) |
G-17 (pmol/L) | 4.55 (2.08–13.96) | 52 (22.61) | 1.95 (1.08–3.85) | 5 (5.05) | < 0.001 |
CEA (ng/mL) | 2.22 (1.36–4.77) | 52 (22.61) | 1.76 (1.13–2.36) | 2 (2.02) | < 0.001 |
CA199 (Uarb/mL) | 10.00 (3.30-24.21) | 46 (20.00) | 4.51(2.33–9.39) | 1 (1.01) | < 0.001 |
CA125 (Uarb/mL) | 11.55 (8.20-17.28) | 19 (8.26) | 9.40 (6.90–13.50) | 2 (2.02) | 0.002 |
GC: gastric cancer |
The value of serum gastrin-17, CEA, CA12-5 and CA19-9 in the diagnosis of gastric cancer
Firstly, we used the normal reference range of our institution as the cutoff values, as a result, we found that the sensitivity of Gastrin-17, CEA, CA125 and CA199 in the diagnosis of GC were 22.61% (95% CI: 17.40%- 28.60%), 22.61% (95% CI: 17.40% − 28.60%), 6.96% (95% CI: 4.00% − 11.10%) and 20.00% (95% CI: 15.00%- 25.80%), respectively, and the corresponding specificity were 94.95% (95% CI: 88.60% − 98.30%), 97.98% (95% CI: 92.90% − 99.80%), 98.99% (95% CI: 94.50% − 100.00%) and 98.99% (95% CI: 94.50% − 100.00%), respectively (Table 3). This suggested that Gastrin-17 had a comparable value as CEA in the diagnosis of GC, which was better than CA125 and CA199.
Table 3
The diagnostic value of Gastrin-17, CEA, CA125 and CA199 in gastric cancer
| Cut-off value | Sen (%) | 95% CI (%) | Spe (%) | 95% CI (%) |
G-17 | 15.00 pmol/L | 22.61 | 17.40–28.60 | 94.95 | 88.60–98.30 |
2.73 pmol/L | 71.30 | 65.00–77.10 | 63.64 | 53.4 0- 73.10 |
CEA | 5.00 ng/mL | 22.61 | 17.40–28.60 | 97.98 | 92.90–99.80 |
3.38 ng/mL | 34.78 | 28.60–41.30 | 93.94 | 87.30–97.70 |
CA125 | 35.00 Uarb/mL | 6.96 | 4.00–11.10 | 98.99 | 94.50–100.00 |
9.70 Uarb/mL | 66.09 | 59.60–72.20 | 53.54 | 43.20–63.60 |
CA199 | 37.00 Uarb/mL | 20.00 | 15.00- 25.80 | 98.99 | 94.50–100.00 |
9.39 Uarb/mL | 52.61 | 45.90–59.20 | 75.76 | 66.10–83.80 |
CI: confidence interval, G-17: gastrin-17, Sen: sensitivity, Spe: specificity |
Then, we derived cutoff values from the ROC by using the MedCalc statistical software as the diagnostic cutoff values for Gastrin-17, CEA, CA125 and CA199, which were 2.73 pmol/L, 3.38 ng/mL, 9.70 Uarb/mL, and 9.39 Uarb/mL, respectively. By using the optimal cutoff values, we found that the sensitivity of Gastrin-17, CEA, CA125 and CA199 in the diagnosis of GC were 71.30% (95% CI: 65.00% − 77.10%), 34.78% (95% CI: 28.60% − 41.30%), 66.09% (95% CI: 59.60% − 72.20%) and 52.61% (95% CI: 45.90% − 59.20%), respectively, and the corresponding specificity were 63.64% (95% CI: 53.40%- 73.10%), 93.94% (95% CI: 87.30% − 97.70%), 53.54% (95% CI: 43.20% − 63.60%) and 75.76% (95% CI: 66.10% − 83.80%), respectively (Table 3). This suggested that Gastrin-17 was most valuable among the four markers in the diagnosis of GC.
Gastrin-17 combined with CEA, CA12-5 and CA19-9 improves the diagnostic value of gastric cancer
In order to compare the diagnostic efficiency of separate and combined tests, we calculated the AUC of ROC curve. As a result, the AUC of G17, CEA, CA125, CA199 were 0.72 (95% CI: 0.67–0.77), 0.64 (95% CI: 0.58–0.69), 0.61 (95% CI: 0.55–0.66) and 0.65 (95% CI: 0.59–0.70), respectively, which showed that G17 had the best diagnostic efficiency among the four markers. By combining the four markers, the AUC increased to 0.79 (95% CI: 0.75–0.84), and the corresponding sensitivity and specificity were 65.22% (95% CI: 58.70% − 71.40%) and 84.85% (95% CI: 76.20% − 91.30%), respectively. This suggested that Gastrin-17 combined with CEA, CA12-5 and CA19-9 could improve the diagnostic accuracy of GC. (Fig. 1, Table 4)
Table 4
Comparison of diagnostic efficiency between separate and combined tests in gastric cancer
| AUC | 95% CI (%) | Sen (%) | 95% CI (%) | Spe (%) | 95% CI (%) |
G17 | 0.72 | 0.67–0.77 | 71.30 | 65.00–77.10 | 63.64 | 53.4 0- 73.10 |
CEA | 0.64 | 0.58–0.69 | 34.78 | 28.60–41.30 | 93.94 | 87.30–97.70 |
CA125 | 0.61 | 0.55–0.66 | 66.09 | 59.60–72.20 | 53.54 | 43.20–63.60 |
CA199 | 0.65 | 0.59–0.70 | 52.61 | 45.90–59.20 | 75.76 | 66.10–83.80 |
G17 + CEA + CA125 + CA199 | 0.79 | 0.75–0.84 | 65.22 | 58.70–71.40 | 84.85 | 76.20–91.30 |
AUC: the area under curve, CI: confidence interval, G-17: gastrin-17, Sen: sensitivity, Spe: specificity |
The association of serum gastrin-17 and clinicopathologic characteristics of gastric cancer
In the 230 GC patients, 152 patients (66.1%) were male and 78 patients (33.9%) were female. One hundred and ninety-eight patients (74.3%) were older than 40 years old, and only 32 patients (25.7%) were younger than 40 years old. Most of the patients had advanced stages with lymph node metastasis. The clinicopathologic characteristics of the included patients were summarized in Table 5.
Table 5
The associations between the level of Gastrin-17 and the characteristics of gastric cancer
| N (%) | G-17 (pmol/L) | P value |
Age | | | 0.489 |
≤ 40 | 32 (13.9) | 4.45 (2.15–7.95) | |
41–65 | 139 (60.4) | 4.56 (2.11–14.82) | |
≥ 66 | 59 (25.7) | 4.43 (1.71–14.38) | |
Gender | | | 0.089 |
Male | 152 (66.1) | 4.18 (1.94–12.33) | |
Female | 78 (33.9) | 5.32 (2.76–18.72) | |
Tumor diameter | | | 0.260 |
< 5cm | 159 (69.1) | 4.54 (1.94–13.21) | |
≥ 5cm | 71 (30.9) | 4.56 (2.29–14.52) | |
Tumor location | | | 0.195 |
Cardia | 9 (3.9) | 8.38 (4.39–24.37) | |
Fundus | 15 (6.5) | 5.92 (1.95–15.63) | |
Body | 51 (22.2) | 7.62 (2.37–21.83) | |
Antrum | 147 (63.9) | 4.03 (1.94–10.10) | |
Diffused | 8 (3.5) | 6.78 (2.41–20.99) | |
Differentiation | | | 0.164 |
Poorly | 157 (68.3) | 4.50 (1.89–12.90) | |
Moderately | 70 (30.4) | 5.78 (2.31–18.39) | |
Well | 3 (1.3) | 4.43 (4.28-) | |
Infiltration depth | | | 0.394 |
T1 | 25 (10.9) | 3.67 (1.88–10.80) | |
T2 | 40 (17.4) | 4.91 (1.77–22.78) | |
T3 | 107 (46.5) | 4.56 (2.17–15.57) | |
T4 | 58 (25.2) | 4.44 (2.17–12.77) | |
Lymph node metastasis | | | 0.158 |
N0 | 60 (26.1) | 4.61 (1.84–10.36) | |
N1-3 | 170 (73.9) | 4.55 (2.27–15.59) | |
Distant metastasis | | | 0.049 |
M0 | 216 (93.9) | 4.38 (1.96–12.52) | |
M1 | 14 (6.1) | 11.23 (7.03–24.92) | |
Pathological stage | | | 0.175 |
Ⅰ | 40 (17.4) | 3.32 (1.66–11.15) | |
Ⅱ | 63 (27.4) | 5.39 (3.14–14.38) | |
Ⅲ | 113 (49.1) | 4.34 (1.98–13.23) | |
Ⅳ | 14 (6.1) | 11.23 (7.03–24.92) | |
G-17: gastrin-17 |
In order to explore the relationship of serum gastrin-17 and clinicopathologic characteristics of gastric cancer, we used the method of univariate analysis. As a result, we found that GC patients with distant metastasis (M1) had a higher level of serum gastrin-17 (P < 0.05, Table 5).