Signet ring cell histology is an independent predictor of poor prognosis in gastric adenocarcinoma: A population-based analysis

ABSTRACT Background To test the hypothesis that signet ring cell (SRC) histology is an independent predictor of poor prognosis in gastric adenocarcinoma regardless of tumoral clinical presentation. Methods We conducted a population-based study to examining the prognostic factors of these two histological subtypes of gastric cancer using data of gastric cancer patients from the Surveillance, Epidemiology, and End Results (SEER) registry between January 2004 and December 2020. Univariate and multivariate Cox regression, and propensity score matching (PSM) models were used to investigate the association between clinical characteristics and prognosis and to calculated hazard ratios (HRs), and corresponding 95% confidence intervals (95% CI). Results Among a total of 38,336 patients, there were 7,979 SRC and 30,357 non-SRC gastric cancer patients. At presentation, SRC significantly differs from non-SRC patients in the distribution of age, sex, race, primary site and stage. Overall, SRC patients confers worse overall survival (OS: HR = 1.21, 95% CI: 1.17-1.24) and cancer-specific survival (CSS: HR = 1.27, 95% CI: 1.23-1.31) than non-SRC patients. Compared with non-SRC gastric cancer, although stage I SRC has overall better survival (mOS: 90 vs 68 months, P < 0.001), however, this better survival of SRC was mainly driven by younger age at diagnosis. After adjusted for age at diagnosis as a continuous variable, early stage SRC patients even has a higher risk of mortality (HR = 1.13, 95% CI: 1.03-1.23 and HR = 1.26, 95% CI: 1.13-1.40 for AJCC stage I and II, respectively). While at advanced stages (stage IV), SRC directly confers worse prognosis and has poorer responses to chemotherapy ( P -heterogeneity < 0.001) in either patients with negative ( P -heterogeneity = 0.009) or positive peritoneal cytology ( P -heterogeneity = 0.055). Conclusion After adjustment of age, SRC confers worse prognosis at all stages. Our study indicates, stage for stage, the SRC histology per se conveys additional risk of mortality. The results support the concept that SRC is a distinct subtype of gastric adenocarcinoma and SRC histology is an independent predictor of poor prognosis for gastric cancer.