Background: There is an ongoing debate over the prognostic value of the number of examined lymph nodes (ELNs) in cases of gastric signet-ring cell cancer (GSRCC). In this study, we sought to evaluate the correlation between the number of ELNs and the prognosis of GSRCC and identify the optimal number of ELNs.

Methods: A total of 1020 patients diagnosed with GSRCC between 2011 and 2018 in the National Cancer Center (NCC) database were identified. Clinicopathological characteristics were retrospectively collected, and the optimal cutoff values of ELNs were calculated using X-tile. The impact of different ELNs on overall survival (OS) was compared using Kaplan‒Meier curves. We used univariate and multivariate Cox and subgroup analyses to explore the relationship between ELNs and OS. Furthermore, nonlinear correlations were investigated using restricted cubic splines (RCSs).

Results: X-tile showed that the optimal cutoff value of ELNs was 22. The 5-year OS was higher for patients with ELNs > 22 (vs. ELNs ≤ 22, 66.9% vs. 74.9%, P = 0.026). Multivariate Cox analyses showed that high ELNs were associated with superior OS (HR=0.56, 95% CI =0.43-0.74, P < 0.001). In subgroup analyses, the significant association between tumor size > 4 cm and TNM III stage was still observed. The RCS regression model showed a U-shaped nonlinear dose–response relationship between ELNs and OS; the inflection point, as well as the lowest risk points, corresponded to 44-52 ELNs.

Conclusion: A U-shaped nonlinear correlation, with inflection points of 44-52 ELNs, between ELNs and prognosis in GSRCC was identified.