Plasma protein biomarkers for the early detection of gastric preneoplasia and cancer: a prospective study

Abstract

Gastric cancer (GC) often presents a poor prognosis due to its asymptomatic phenotype at early stages. Upper endoscopy, the current gold standard for diagnosis, is invasive with limited sensitivity for detecting gastric preneoplasia. Non-invasive biomarkers, such as blood circulating proteins offer a promising alternative for an early detection. Using mass spectrometry-based proteomics we identified plasma proteins as biomarkers of the presence of gastric preneoplasia and cancer lesions in an exploratory subgroup of patients (n=39). Fifteen promising protein candidates emerged to distinguish patient categories and were further confirmed by enzyme-linked immunosorbent assays (ELISA) in plasma samples from a cohort of 138 participants. Our predictive models demonstrated high classification performance with a minimal set of biomarkers, making them clinically applicable. Repeated cross-validations yielded high Area Under the Receiver Operating Characteristics (AUROC) values, notably distinguishing cancerous or precancerous cases from non-cancerous ones. Leveraging simple blood sampling, this strategy holds promise to detect high-risk gastric lesions, even at asymptomatic stages. Such an approach could significantly improve early detection and clinical management of GC, offering direct benefit for patients.