Validation of Circulating miRNA Biomarkers for Predicting Lymph Node Metastasis in Gastric Cancer

We validated candidate biomarkers using circulating miRNAs by analyzing serum miRNA concentrations from patients with gastric cancer (GC) to predict lymph node (LN) metastasis. In a pilot study, serum levels of miR-21, miR-27a, miR-106b, miR-146a, miR-148a, miR-223, and miR-433 were compared in 10 healthy donors, 16 LN-positive patients with GC, and 15 LN-negative patients with GC. Then, we compared the Level of three miRNAs (miR-21, miR-146a, and miR-148a) with the total of 79 GC patients with or without LN metastasis. In the pilot study, miR-21, miR-27a, miR-106b, miR-146a, miR-148a, and miR-223 concentrations from LN-positive patients with GC were significantly different from those of LN-negative patients with GC (P < 0.001, P = 0.003, P = 0.033, P < 0.001, P < 0.001, and P = 0.017, respectively). In the validation study, levels of miR-21, miR-146a, and miR-148a increased as pN stage increased (P < 0.001, P = 0.001, and P < 0.001, respectively). Levels of the miRNAs were significantly different between pN0 and pN0 in the pT1 group (P = 0.013, P = 0.004, and P = 0.035, respectively) and among clinical stages (P = 0.001, P = 0.002, and P <0.001, respectively). No differences in miRNA levels were observed by pT stage, Lauren's classification, sex, or age. Serum concentrations of miR-21, miR-146a, and miR-148a were closely associated with GC pN stage. These serum miRNA Levels could be biomarker candidates to predict the presence of LN metastasis.