Cellular senescence in gastric cancer: a novel prognostic stratification and immune predictor.

[UNLABELLED] Cellular senescence, a state of permanent arrest of the cell cycle in response to various damage, exerts dual impact on tumor initiation and progression and has emerged as a promising therapeutic target. However, an applicable tool to quantify senescence remains exclusive. In this study, we investigated the role of senescence in gastric cancer (GC) progression through the analysis of TCGA-STAD cohort. According to senescence-associated gene (SAG) expression signatures, TCGA-STAD was divided into distinct senescence clusters. Cluster B with elevated expression of SAGs was associated with a poorer prognosis and a tumor microenvironment that was more conducive for tumor growth. Based on prognosis-associated differentially expressed genes (DEGs) between senescence clusters, we constructed cellular senescence score system (SSS) to quantify senescence of GC. SSS could serve as an independent prognostic factor and, notably, has the potential to identify patients who may benefit from immunotherapy. This indicates the strong potential of SSS as a biomarker for predicting immunotherapeutic response. In conclusion, SSS provides a reliable tool for prognosis prediction and treatment strategies for GC patients.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s12920-026-02346-1.