Study population
From November 2009 to December 2018, 797 patients were enrolled in our research. A total of 722 (90.6%) gastric adenocarcinoma cases (non-HAS) and 75 (9.4%) HAS cases were detected by histological morphology and immunohistochemistry. Through one-to-one nearest-neighbour matching with a 0.02 calliper width, 144 patients were included for analysis, with 72 HAS and non-HAS patients each. Through one-to-two nearest-neighbour matching with a 0.05 calliper width, 165 patients were included in our study, with 110 non-HAS patients and 55 HAS patients.
Clinicopathological Characteristics
For the 797 patients, the two groups (HAS and non-HAS) were consistent in terms of sex, age, tumour location, surgery type, vascular invasion, and N and M classification. Nevertheless, the two groups were differentially distributed in terms of T classification, EGFR, KI-67, CEA, CA199, HER-2 and neoadjuvant chemotherapy. One-to-one and one-to-two nearest-neighbour matching were used to generate 144 and 165 patients from the two groups, respectively. They showed no significant bias in clinicopathological characteristics (Table 1). Before matching, 11.8% (85/722) of patients with non-HAS received neoadjuvant chemotherapy, and 24% (18/75) with HAS received neoadjuvant chemotherapy. In the 1:1 propensity score matching group, the proportion of patients with non-HAS and HAS was 27.8% (20/72) and 22.2% (16/72), respectively. In the 1:2 propensity score matching group, the proportion of patients who underwent neoadjuvant chemotherapy was 15.5% (17/110) and 16.4% (9/55), respectively.
Survival Among All Patients And Propensity-matched Pairs
In our analysis, we found that OS was not significantly different between the HAS group and the non-HAS group (Fig. 1). Among the 797 patients in our study, the 1-, 2-, and 3-year survival rates of non-HAS patients were 92.2%, 80.7%, and 74.2%, and those of HAS patients were 93.1%, 86.8%, and 85.0%, respectively. Among the one-to-one nearest-neighbour matched pairs of patients, the 1-, 2-, and 3-year survival rates of non-HAS patients were 94.4%, 86.5%, and 82.3%, and those of HAS patients were 92.9%, 86.3% and 84.5%, respectively. Among one-to-two nearest-neighbour matched pairs of patients, the 1-, 2-, and 3-year survival rates of non-HAS patients were 98.1%, 98.1%, and 96.9%, and those of HAS patients were 90.3%, 83.9% and 79.9%, respectively.
Risk Factors For Prognosis
Among the 797 patients, univariate analysis showed that the tumour location, surgery type, TNM stage, levels of CEA and CA19-9, EGFR expression, and neoadjuvant chemotherapy were significantly associated with OS. Among the one-to-one nearest-neighbour matched pairs of patients, T and M stage, EGFR expression and neoadjuvant chemotherapy were found to be significantly related to OS. Among the one-to-two propensity-matched pairs of patients, T and M stage, level of CEA and EGFR expression were significantly associated with OS (Table 2).
Table 2
Univariate analyses of OS was using the Kaplan-Meier approach and p (log rank (Mantel-Cox)) < 0.05 served as the threshold of significance
Factors(k-m) | Before propensity matching p value* | | After 1:1 propensity matching p value | | After 1:2 propensity matching p value |
| OS | | OS | | OS |
GC typesa | 0.490 | | 0.345 | | 0.195 |
Age | 0.158 | | 0.277 | | 0.446 |
Sex | 0.964 | | 0.584 | | 0.322 |
Location | 0.003 | | 0.903 | | 0.555 |
Surgery type | < 0.001 | | 0.530 | | 0.471 |
Vascular invasion | < 0.001 | | 0.120 | | 0.101 |
T | < 0.001 | | 0.001 | | 0.013 |
N | < 0.001 | | 0.201 | | 0.431 |
M | < 0.001 | | < 0.001 | | < 0.001 |
CEA | 0.002 | | 0.066 | | < 0.002 |
CA199 | < 0.001 | | 0.552 | | 0.312 |
EGFR | < 0.001 | | < 0.001 | | 0.007 |
HER2 | 0.520 | | 0.397 | | 0.644 |
KI-67 | 0.291 | | 0.067 | | 0.258 |
Neoadjuvant chemotherapy | 0.008 | | 0.043 | | 0.08 |
a GC types: hepatoid adenocarcinoma of the stotmach and non-hepatoid adenocarcinoma of the stomach |
*Log Rank (Mantel-Cox) |
Among the 797 patients, multivariate analysis identified prognostic factors, including TNM stage and level of CA19-9 (Table 3a). Among the one-to-one nearest-neighbour matched pairs of patients, univariate analysis identified some factors significantly related to OS, including T stage, M stage, and neoadjuvant chemotherapy (Table 3b). Among the one-to-two nearest-neighbour matched pairs of patients, the GC type is solely associated with OS (Table 3c).
Table 3
Multivariable survival analysis to identify factors predicting OS by using Cox proportional hazards model
a | Before propensity matching |
Factor | HR | 95%CI | P value |
GC type non-HAS HAS | - 1.377 | - 0.706–2.687 | - 0.348 |
Age(yr) <45 60 > age ≥ 45 ≥ 60 | - 1.301 1.621 | - 0.733–2.310 0.918–2.862 | 0.185 - 0.369 0.096 |
Location U M L T | - 0.912 1.056 1.242 | - 0.569–1.461 0.592–1.885 0.431–3.577 | 0.914 - 0.703 0.853 0.688 |
Surgery type PG DG TG TGC | - 1.133 1.810 5.152 | - 0.142–9.039 0.243–13.473 0.431–61.637 | 0.155 - 0.906 0.562 0.195 |
Vascular invasion no yes | - 1.152 | - 0.778–1.705 | 0.480 |
T Tis,T0,T1,T2 T3 T4 | - 1.940 3.645 | - 0.946–3.980 1.817–7.314 | < 0.001 - 0.071 < 0.001 |
N N0 N1 N2 N3 | - 1.827 2.058 3.649 | - 0.924–3.613 1.034–4.095 1.885–7.066 | < 0.001 - 0.083 0.040 < 0.001 |
M M0 M1 | - 2.253 | - 1.061–4.781 | - 0.034 |
CEA(ng/ml) ≤5 >5 | - 1.403 | - 0.969–2.031 | - 0.073 |
CA199(u/ml) ≤37 >37 | - 1.537 | - 1.022–2.309 | - 0.039 |
EGFR - + ++ +++ | - 1.315 0.727 0.736 | - 0.774–2.234 0.381–1.387 0.386–1.404 | 0.026 - 0.312 0.334 0.352 |
Neoadjuvant chemotherapy no yes | - 1.504 | - 0.982–2.304 | - 0.061 |
b After 1:1 propensity matching |
Factor | HR | 95%CI | P |
GC type non-HAS HAS | - 1.230 | - 0.461–3.278 | - 0.679 |
Age(yr) <45 60 > age ≥ 45 ≥60 | - 1.155 2.615 | - 0.128–10.450 0.312–21.887 | 0.206 - 0.898 0.375 |
Vascular invasion no yes | - 3.224 | - 0.623–16.685 | - 0.163 |
T Tis,T0,T1,T2 T3 T4 | - 3.450 8.497 | - 0.631–18.861 1.481–48.738 | 0.033 - 0.153 0.016 |
N N0 N1 N2 N3 | - 0.102 0.325 0.222 | - 0.025–1.396 0.052–2.670 0.037–2.149 | 0.408 - 0.102 0.325 0.222 |
M M0 M1 | - 8.187 | - 1.980-33.846 | - 0.004 |
EGFR - + ++ +++ | - 0.212 0.069 0.208 | - 0.018–2.466 0.006–0.798 0.018–2.458 | 0.082 - 0.215 0.032 0.213 |
Neoadjuvant chemotherapy no yes | - 3.031 | - 1.165–7.882 | - 0.023 |
c After 1:2 propensity matching |
Factor | HR | 95%CI | P |
GC type non-HAS HAS | - 3.348 | - 1.124–9.977 | - 0.030 |
Age(yr) <45 60༞age ≥ 45 ≥60 | - 5.775 7.356 | - 0.167-200.111 0.248–217.980 | 0.466 - 0.332 0.248 |
Vascular invasion no yes | - 2.909 | - 0.521–16.247 | - 0.224 |
T Tis,T0,T1,T2 T3 T4 | - 5.353 7.229 | - 0.749–38.243 0.898–58.202 | 0.171 - 0.095 0.063 |
N N0 N1 N2 N3 | - 0.583 0.337 0.724 | - 0.069–4.959 0.034–3.335 0.088–5.931 | 0.730 - 0.621 0.352 0.764 |
M M0 M1 | - 69.379 | - 3.009-1599.499 | - 0.008 |
CEA(ng/ml) ≤5 >5 | - 7.077 | - 2.018–24.815 | - 0.002 |
EGFR - + ++ +++ | - 0.077 0.077 0.107 | - 0.008–0.755 0.008–0.779 0.014-0.800 | 0.122 - 0.028 0.030 0.029 |
Neoadjuvant chemotherapy no yes | - 2.169 | - 0.641–7.338 | - 0.213 |