Circulating miR-19, miR-27a, and miR-200c as novel biomarkers for resistance to neoadjuvant chemotherapy in gastric cancer patients: a pilot study

Background Neoadjuvant chemotherapy (NAC) is a standard approach for treating locally advanced gastric cancer (GC), but resistance in some patients can result in treatment toxicity and surgical delays without therapeutic benefit. Identifying biomarkers predictive of NAC response is crucial for personalized treatment strategies. This study evaluated circulating microRNAs (miRNAs) as potential biomarkers for NAC response. Materials and methods Plasma samples from 39 GC patients undergoing NAC followed by gastrectomy (NCT04223401) were collected before treatment. Four miRNAs (miR-19a, miR-21, miR-27a, miR-200c) were analyzed via quantitative real-time polymerase chain reaction. NAC response was assessed in histological specimens using the Becker tumor regression grade (TRG), which classifies patients as Responders (TRG 1-2) or Non-responders (TRG 3). Results Among 39 patients, 20 (51%) were Responders, and 19 (49%) were Non-responders. miR-19a, miR-21, and miR-200c were significantly upregulated in Non-responders (p < 0.05). ROC analysis revealed miR-19a (AUC: 0.693), miR-21 (AUC: 0.700), and miR-200c (AUC: 0.772) as predictive of resistance. Univariate analysis revealed a correlation between higher levels of miR-19a, miR-21, and miR-200c and a low neutrophil count, with increased resistance risk. Multivariate analysis confirmed miR-200c as an independent predictor of resistance (OR: 20.90; 95% CI: 1.54-283.73). Conclusions This pilot study identifies circulating miR-19a, miR-21, and miR-200c as novel biomarkers for poor NAC response in GC, providing a foundation for personalized treatment strategies.