Characterization of senescence-associated secretory phenotype-related genes and construction of a prediction model in gastric cancer

Gastric cancer (GC) remains one of the most lethal digestive malignancies, with limited biomarkers available for risk stratification and therapeutic decision-making. The senescence-associated secretory phenotype (SASP) has been implicated in various cancer-related processes, but its prognostic value in GC has not been fully explored. We characterized diverse landscapes of differentially expressed SASP-related genes and developed a prognostic gene signature, the SASP index (SASPI), through Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis. We collected transcriptomic, genomic, and clinical information from The Cancer Genome Atlas stomach adenocarcinoma cohort (TCGA-STAD) and three Gene Expression Omnibus (GEO) cohorts, namely GSE62254, GSE66229, and GSE84437, to build and validate the predictive efficacy of the SASPI-related prediction model. High SASPI was associated with poorer prognosis and was significantly linked to the upregulation of biological pathways that drive tumor aggressiveness, such as epithelial-mesenchymal transition (EMT) and angiogenesis. Furthermore, SASPI correlated with distinct drug sensitivity patterns and immunological profiles. Specifically, individuals in the high-SASPI group exhibited decreased sensitivity to chemotherapeutic agents like 5-fluorouracil, oxaliplatin, and paclitaxel, and exhibited an inflamed but immunologically dysfunctional phenotype. The findings highlight that the SASPI could serve as a novel biomarker for risk stratification and prognosis in GC, offering new insights into the molecular drivers of tumor progression and potential therapeutic targets.