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Context: The sensitivity and specificity of blood microRNA-421 (miR-421) as a gastric cancer (GC) biomarker has not been determined. Objective: To investigate the diagnostic value of blood miR-421 as GC biomarker. Materials and methods: miR-421 in serum and peripheral blood mononuclear cells (PBMCs) of 90 GC patients and 90 controls was detected by quantitative real-time PCR. The correlation of miR-421 to GC clinicopathological features as well as the diagnostic value of miR-421 comparing to carcinoembryonic antigen (CEA) and cancer antigen 125 (CA-125) were analyzed. Results: miR-421 increased significantly in GC patients than in controls. miR-421 in either serum or PBMCs had higher sensitivity and specificity than CEA and CA-125 in GC diagnosis. The GC positive prediction rates of miR-421 were also significantly higher than those of CEA and CA-125. Discussion and conclusions: miR-421 in serum or PBMCs may be a new potential diagnostic biomarker for GC. [ABSTRACT FROM AUTHOR]