Propofol anesthesia for gastric cancer surgery increased cancer suppressor miR-122-5p expression in plasma extracellular vesicles compared with sevoflurane

Abstract Objectives The impact of anesthetic drugs on cancer cells is controversial. As propofol and sevoflurane are widely used in gastric cancer surgery, this study aimed to investigate their effects on microRNA (miRNA) expression in plasma extracellular vesicles (EVs) and on circulating gastric cancer cells during surgery. Methods We collected the plasma of 10 patients with gastric adenocarcinoma who were anesthetized with propofol or sevoflurane for sequencing. Differentially expressed miRNAs were screened via DESeq2 and verified by qPCR in another 18 paired samples from nine patients before and after propofol anesthesia. Plasma EVs were stained with PKH26 and cocultured with GES-1 and AGS cells, and miR-122-5p expression was determined. The target genes were analyzed using MiRanda/RNAhybrid/KEGG/KM plotter. Results 19 (13 upregulated/6 downregulated) and 5 (2 upregulated/3 downregulated) differentially expressed miRNAs were identified after propofol and sevoflurane, respectively. MAPK, AKT1, AKT2, and EGFR were the target genes of the propofol-upregulated miRNAs. miR-122-5p expression in the plasma EVs of patients after propofol increased by an average of 6.2-fold (p=0.011). After coculture, hsa-miR-122-5p expression was significantly greater in both the GES-1 and AGS cell lines than in the control group. High expression of the hsa-miR-122-5p target gene PPP2R2D was significantly correlated with reduced overall survival (hazard ratio [HR] = 1.56, p=5.5 × 10 −5 ), whereas high expression of PPP2R5B predicted poorer survival (HR=1.41, p=6.7 × 10 −5 ). Conclusions miR-122-5p in plasma EVs was affected by propofol and serves as an inhibitor of gastric cancer.