MiRNA-199a-3p in Plasma as a Potential Diagnostic Biomarker for Gastric Cancer

Background. MicroRNA (miRNA) has been shown the potential of cancer diagnosis. We investigated whether plasma miRNA expression could discriminate between patients with and without gastric cancer. Methods. This study was divided into three steps: (1) miRNA microarray profiling on plasma samples from 20 gastric cancer patients and 20 healthy controls; (2) miRNA selection by real-time qRT-PCR on 30 pairs of plasma from patients and controls; and (3) qRT-PCR validation on an independent set of plasma from 180 gastric cancer patients, 80 healthy controls, and 20 patients with gastric precancerous diseases. Results. Of the 959 human miRNAs analyzed by microarray, 37 up-regulated miRNAs and seven down-regulated miRNAs were found in gastric cancer plasma. Of the seven discrepant miRNAs validated on the plasma from 30 gastric cancer patients and 30 healthy controls, both miRNA-199a-3p and miRNA-151-5p were significantly elevated (P < 0.05) and were significantly reduced after surgery (P < 0.05) in gastric cancer patients. Further large-scale validation showed that these two miRNAs expressions in plasma were significantly higher in gastric cancer patients than healthy controls and patients with gastric precancerous diseases, respectively. However, only the expression of miRNA-199a-3p in plasma was significantly associated with tumor invasion and with lymph node metastasis and tumor, node, metastasis stage. This marker yielded an area under the receiver operating characteristic curve area of 0.837 with 80 % sensitivity and 74 % specificity in discriminating gastric cancer patients from healthy controls. In gastric cancer tissue, miRNA-199a-3p was expressed in the cytoplasm of tumor cells. Conclusions. miRNA-199a-3p in plasma could be a novel potential diagnostic biomarker for gastric cancer detection.