Serum microRNAs as potential new biomarkers for cisplatin resistance in gastric cancer patients

Abstract

Background microRNAs (miRNAs) have been studied for their role in the early detection of several diseases. However, there is no current information on the systematic screening of serum-derived cisplatin resistance biomarkers in gastric cancer (GC). Methods Cisplatin-resistant GC cell lines were screened for dysregulated miRNAs using small RNA sequencing (sRNA-seq) and miRNAs were functionally annotated using bioinformatics analyses. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to validate the miRNA-relative transcription levels in GC cells and in 74 GC patients. We analyzed the associations between the clinical characteristics of the patients and their miRNA expression. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic value for serum-derived cisplatin resistance. Results Seven miRNAs were identified from 35 differentially expressed miRNAs between the MGC803/DDP and MGC803 cells in a public database. We found four miRNA candidates (miR-9-3p, miR-9-5p, miR-146a-5p, and miR-433-3p) that were significantly associated with chemotherapy responses in GC cells and patients. miR-9-5p (AUC = 0.856, 95% CI [0.773–0.939], p < 0.0001) and a combined group (miR-9-5p + miR-9-3p + miR-433-3p) (AUC = 0.915, 95% CI [0.856–0.975], P < 0.0001) distinguished chemoresistant GC patients from chemosensitive GC patients. Conclusions Our study reveals the potential therapeutic use of two serum-based biomarkers, miR-9-5p and a combined group (miR-9-5p + miR-9-3p + miR-433-3p), as indicators for the successful use of cisplatin in GC patients.