Aptamer Interfaces for Serum-Based Gastric Cancer Detection: From Molecular Recognition to Clinical Decision

Gastric cancer is the fifth most commonly diagnosed malignancy and the fifth leading cause of cancer death worldwide, and it remains lethal chiefly because it is detected late. Endoscopic screening demonstrably works where it is deployed at scale, but endoscopy cannot be extended to the several hundred million people who would need it; a blood test that stratifies risk before endoscopy is therefore the only realistic route to population-level early detection. Aptamers-short, chemically synthesizable nucleic acid ligands-are attractive recognition elements for such a test, and more than a decade of work has produced hundreds of aptasensors that detect gastric cancer serum markers with impressive analytical sensitivity. Almost none has reached clinical use. Here we argue that this impasse is not a problem of affinity, nor of limit of detection, but of interface design. We resolve aptamer-based serum diagnostics into four coupled interfaces-molecular recognition, the serum matrix, signal transduction and clinical evidence-and show that each has been optimized locally while the constraints they impose jointly have been ignored. We then specify a reference architecture and a minimum evidence standard for a gastric cancer serum aptamer test, and identify the five measurements that would move the field from demonstration to deployment.