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Crosstalk between pyroptosis and tumor immune microenvironment (TIME) in cancer has yet to be elucidated. Herein, we aimed to explore the role of pyroptosis and its association with TIME in gastric cancer. Unsupervised clustering was performed to identify the pyroptosis-related clusters. Pyroptosis risk score was constructed using LASSO Cox regression. Clinicopathological and genetic data of pyroptosis clusters and pyroptosis risk scores were explored. Reproducibility of pyroptosis risk score in predicting response to immunotherapy and screening potential antitumor drugs was also investigated. Three pyroptosis clusters with distinct prognosis, immune cell fractions and signatures, were constructed. A low-pyroptosis risk score was characterized by increased activated T-cell subtype and M1 macrophage, decreased M2 macrophage, higher MSI status, and TMB. Meanwhile, low-score significantly correlated with PD-L1 expression, antigen presentation markers, and IFN-γ signature. The 5-year AUCs of PRS were 0.67, 0.62, 0.65, 0.67, and 0.67 in the TCGA, three external public and one real-world validation (SYSUCC) cohorts. Multivariable analyses further validated the prognostic performance of the pyroptosis risk scoring system, with HRs of 2.43, 1.83, 1.78, 2.35, and 2.67 (all p < 0.05) in the five cohorts. GSEA indicated significant enrichment of DNA damage repair pathways in the low-score group. Finally, the pyroptosis risk scoring system was demonstrated to be useful in predicting response to immunotherapy, and in screening potential antitumor drugs. Our study highlights the crucial role of interaction between pyroptosis and TIME in gastric cancer. The pyroptosis risk scoring system can be used independently to predict the survival of individuals and their response to immunotherapy.

Background: Dysregulation of lipid metabolism plays important roles in the tumorigenesis and progression of gastric cancer (GC). The present study aimed to establish a prognostic model based on the lipid metabolism–related genes in GC patients.Materials and Methods: Two GC datasets from the Gene Expression Atlas, GSE62254 (n = 300) and GSE26942 (n = 217), were used as training and validation cohorts to establish a risk predictive scoring model. The efficacy of this model was assessed by ROC analysis. The association of the risk predictive scores with patient characteristics and immune cell subtypes was evaluated. A nomogram was constructed based on the risk predictive score model and other prognostic factors.Results: A risk predictive score model was established based on the expression of 19 lipid metabolism–related genes (LPL, IPMK, PLCB3, CDIPT, PIK3CA, DPM2, PIGZ, GPD2, GPX3, LTC4S, CYP1A2, GALC, SGMS1, SMPD2, SMPD3, FUT6, ST3GAL1, B4GALNT1, and ACADS). The time-dependent ROC analysis revealed that the risk predictive score model was stable and robust. Patients with high risk scores had significantly unfavorable overall survival compared with those with low risk scores in both the training and validation cohorts. A higher risk score was associated with more aggressive features, including a higher tumor grade, a more advanced TNM stage, and diffuse type of Lauren classification of GC. Moreover, distinct immune cell subtypes and signaling pathways were found between the high–risk and low–risk score groups. A nomogram containing patients’ age, tumor stage, adjuvant chemotherapy, and the risk predictive score could accurately predict the survival probability of patients at 1, 3, and 5 years.Conclusion: A novel 19-gene risk predictive score model was developed based on the lipid metabolism–related genes, which could be a potential prognostic indicator and therapeutic target of GC.

BackgroundAccording to the 8th edition AJCC staging manual, a least of 16 lymph nodes retrieval (LNRs) is the minimal requirement for lymph nodes (LNs) dissection of gastric cancer surgery. Previous studies have shown that increasing the number of LNRs (≥30) prolongs survival for selected patients. However, the necessity of retrieving 30 or more LN for stage II gastric cancer patients is still under debate.AimThis study aims to explore the impact of retrieving 30 or more lymph nodes on the survival of stage II cancer patients.MethodsA total of 1,177 patients diagnosed with stage II gastric cancer were enrolled in this study. The clinicopathological parameters and the impact of different LNRs (60 years/male/underwent total gastrectomy/stage IIB. For N+ patients, higher NR was significantly correlated with poor survival.ConclusionThe survival benefit of retrieving 30 LNs varies in different subgroups. An LNRs of 30 is mandatory for selected stage II gastric cancer patients.