Diagnostic Value of Serum CFL1 and TAGLN2 for Non-Metastatic Gastric Cancer: A Retrospective and Prospective Real-World Study

<b>Background</b>: Timely screening and diagnosis are critical for improving prognosis and survival in gastric cancer. Building on prior serum proteomics findings, this study evaluated two novel early-stage diagnostic biomarkers, CFL1 and TAGLN2, using retrospective and prospective cohorts. <b>Methods</b>: Retrospective analysis included 176 non-metastatic gastric cancer patients, 88 healthy controls, and patients with non-gastric non-metastatic cancers/malignancies (<i>n</i> = 143). A prospective study enrolled 88 gastroenterology patients with unknown cancer status before sampling; conventional markers, including CEA, AFP, CA199, and CA125, were measured for comparison. <b>Results</b>: Retrospectively, CFL1 and TAGLN2 achieved approximately 80% sensitivity and >70% accuracy in distinguishing gastric cancer from controls. Prospectively, both markers reached 87.5% sensitivity and 100% specificity, with high NPV and low negative likelihood ratio, supporting their potential for early screening. CFL1 showed higher disease specificity and pre-analytical stability than TAGLN2 across multiple non-gastric cancers and special-condition samples. <b>Conclusions</b>: A combined panel with routine markers improved calibration and decision-curve benefit, suggesting that multi-marker testing can enhance risk stratification and screening efficiency.