Identification and validation VAT1 in gastric cancer through bioinformatics and experimental analysis

•VAT1 is overexpressed in gastric cancer and serves as an independent prognostic marker.•In vitro and in vivo assays show VAT1 promotes tumor cell proliferation and suppresses apoptosis.•VAT1 is involved in the MAPK signaling pathway and EMT.•VAT1 correlates with macrophage infiltration and reduced chemotherapy sensitivity, serving as a biomarker and therapeutic target. This study investigated the expression pattern of Vesicular Amine Transporter 1 (VAT1) in gastric cancer (GC) and its impact on prognosis, alongside evaluating its potential as a biomarker for immunotherapy and chemotherapy. Analysis of transcriptomic data, supported by experimental validation, revealed that VAT1 is highly expressed in GC and is associated with poor prognosis. Kaplan-Meier and ROC analyses demonstrated VAT1′s potential in GC diagnosis, while multivariate analysis confirmed its role as an independent risk factor. Gene set enrichment analysis indicated that VAT1 plays a role in regulating the MAPK signaling pathway and epithelial-mesenchymal transition (EMT) in GC. Immune infiltration analysis showed a positive correlation between VAT1 and immune cells, particularly macrophages, and a negative correlation with chemotherapy sensitivity. In vitro and in vivo experiments further confirmed VAT1′s critical role in promoting GC cell proliferation and inhibiting apoptosis. Overall, VAT1 holds significant value not only in GC diagnosis and prognosis but also as a potential target for immunotherapy and overcoming drug resistance.