Abstract
BACKGROUND: Serum Cystatin S (CST4), a secretory protein that inhibits cellular matrix degradation, significantly influences the tumor microenvironment and tumor progression. However, the prognostic value of serum CST4 in gastric cancer (GC) remains unclear. This study aims to explore serum CST4's utility in GC prognostic assessment. METHODS: A cohort of 334 patients with GC who underwent radical gastrectomy was assessed. Preoperative serum CST4 levels were measured alongside traditional tumor markers, correlating with clinical data and patient outcomes. The cohort was divided into training and test sets at a ratio of 3:1 for Cox regression analyses, which identified CST4 as an independent risk factor for overall survival (OS) and disease-free survival (DFS). A prognostic model was developed, validated with calibration curves, and its predictive value was evaluated using receiver operating characteristic (ROC) curves. In addition, CST4 expression was correlated with immune cell infiltration using data from The Cancer Genome Atlas (TCGA). Patients were stratified by median CST4 levels, and Kaplan-Meier curves for OS and DFS were plotted. RESULTS: Cystatin S was confirmed as an independent risk factor for OS and DFS. Integrating CST4 with traditional markers and TNM pathological staging significantly enhanced the predictive value for prognosis. Cystatin S's impact on tumor progression is likely mediated through modulation of the immune microenvironment, including immune suppression and evasion. CONCLUSION: Cystatin S is an effective biomarker for GC prognostic assessment, assisting in the evaluation of prognosis and the selection of treatment strategies for patients with GC.