Abstract
OBJECTIVE: A risk-based sequential screening strategy, from questionnaire-based assessment to biomarker measurement and then to endoscopic examination, has the potential to enhance gastric cancer (GC) screening efficiency. We aimed to evaluate the ability of five common stomach-specific serum biomarkers to further enrich high-risk individuals for GC in the questionnaire-identified high-risk population. METHODS: This study was conducted based on a risk-based screening program in Ningxia Hui Autonomous Region, China. We first performed questionnaire assessment involving 23,381 individuals (7,042 outpatients and 16,339 individuals from the community), and those assessed as "high-risk" were then invited to participate in serological assays and endoscopic examinations. The serological biomarker model was derived based on logistic regression, with predictors selected via the Akaike information criterion. Model performance was evaluated by the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 2,011 participants were ultimately included for analysis. The final serological biomarker model had three predictors, comprising pepsinogen I (PGI), pepsinogen I/II ratio (PGR), and anti-Helicobacter pylori immunoglobulin G (anti-H. pylori IgG) antibodies. This model generated an AUC of 0.733 (95% confidence interval: 0.655-0.812) and demonstrated the best discriminative ability compared with previously developed serological biomarker models. As the risk cut-off value of our model rose, the detection rate increased and the number of endoscopies needed to detect one case decreased. CONCLUSIONS: PGI, PGR, and anti-H. pylori IgG could be jointly used to further enrich high-risk individuals for GC among those selected by questionnaire assessment, providing insight for the development of a multi-stage risk-based sequential strategy for GC screening.