3.1 Clinicopathological characteristics
Of 859 patients identified with pancreatic SRCC, 120 patients were finally included in our study . There were 64 males (53.3%) and 56 females (46.7%) with the median age of was 67 years (IQR,58.3-75.0 years). Tumor was located at pancreatic head (12.5%), at body or tail(79.2%). Poorly differentiation and undifferentiation (n =95, 79.2%) was the most common tumor grade, followed by moderate differentiation (n = 18, 15.0%). More than half of patients (75; 62.5%) had lymph node metastasis was compared with 45 (37.5%) patients without metastasis. 41 patients (22.6%) received radiotherapy while 64 patients (53.3%) had received chemotherapy. 1-7 lymph nodes were examined in 37 patients(30.8%) and at least 8 lymph nodes were examined in 83 patients(69.2%). The detailed baseline characteristics were displayed in Table 1.
3.2 Correlations between LNR and clinicopathologic characteristics
The median LNR of all patients was 0.106(IQR, 0–0.273).We divided the entire cohort into
the low-risk cohort(LNR <0.20) and high-risk cohort(LNR≥0.20) according to the result analyzed by X-tile software.76 patients were included into the low-risk cohort(LNR <0.20) while 44 patients constitute the high-risk cohort(LNR≥0.20).It was statistically significant that LNR was correlated with tumor grade(P=0.023),location(0.017),N stage(6th)(P<0.001) and nodal status(P<0.001).
3.3 High level of LNR and low level of TNLE is related with poor survival
As is shown in the figure 1 and figure 2, 8 and 0.20 were the cutoff value of TNLE and LNR respectively. The Kaplan-Meier curves showed that there were significant differences of OS rates of LNR and TNLE(P<0.05).According to the result of OS, it showed that higher level of LNR and low level of TNLE for patients with resected pancreatic signet ring cell carcinoma has a worse survival(Fig. 3A,3B).With the further stratified data analysis, when TNLE was at least 8, LNR was able to distinguish the survival difference of patients with resected pancreatic signet ring cell carcinoma in the OS analysis(Fig. 3C,3D).
3.4 Prognostic significance of chemotherapy
In the total cohort, patients with resected pancreatic signet ring cell carcinoma are more likely to acquire chemotherapy(64/120) rather than radiotherapy(41/120).There were no significant differences in OS of radiotherapy(P>0.05,Fig4A). The overall median survival time of patients with resected pancreatic signet ring cell carcinoma who do not acquire chemotherapy was just 10 months and who acquire chemotherapy was just 16 months. Chemotherapy can statistically improve survival in OS analyses(P<0.05, Fig4B).
3.5 Univariate and multivariate analyses
The median OS of pancreatic SRCC was 12 months (IQR,6-29months) and the 1-year ,3-year ,5-year OS rates were 52.4%, 20.8% and 16.6% respectively. In the univariate analysis, age ( P = 0.019), grade (P = 0.001), chemotherapy(P=0.009), LNR(P=0.006), TNLE(P=0.010) were significantly associated with OS, while race, sex, tumor location, TNM staging, T stage, N stage(6th), nodal status, radiotherapy were not significantly related to OS (P > 0.05).
Variables that were significantly associated with OS analyzed by multivariate analyses were
selected to be prognostic indicators (Table 3).After adjusting for other risk factors in the model for LNR of multivariate survival analysis, LNR(P=0.010, HR =1.178, 95% CI: 1.149 to 2.756) and grade(P=0.011, HR =2.481, 95% CI:1.230-5.002) were considered as the independent prognostic indicator. In the model for TNLE of multivariate analysis, grade(P=0.010, HR =2.512, 95% CI:1.246-5.064) was considered as the independent prognostic indicator while TNLE(P=0.060, HR =0.643, 95% CI:0.406-1.019) was not.
3.6 Total number of lymph node examined and nodal status
Total number of lymph node examined and nodal status are important to identify the N stage. To further clarify the optimal value of TNLE, ROC analysis was used to investigate the discriminatory ability of total number of lymph node examined among the patients who had no LNM(N0), and also patients who had at least 1 LNM(N1 6th). As is shown in the figure 5, TNLE 8 showed the highest discriminatory power(AUC 0.656, 95%CI 0.564-0.741, Youden index 0.2533, sensitivity 78.67%, specificity 46.67%, P= 0.003).Even though in our univariate analysis, N stage(6th) and nodal status were not prognostic factors (Fig 6A,7A) while TNLE was not the independent prognostic indicator. In the further stratified data analysis, we find that when TNLE was ≥8, N stage(6th),N stage(8th) show their prognostic significance of patients with resected pancreatic signet ring cell carcinoma(Fig 6C,7C,P<0.05).Combined with these above result, 8 was the optimal cutoff value of the number of lymph node examined to identify the N stage.