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.

Association of the Epithelial–Mesenchymal Transition (EMT) with Cisplatin Resistance

“…CP is a key member of platinum compounds with excellent anti-tumor activity against different cancers such as breast cancer, prostate cancer, bladder cancer, lung cancer, brain tumors, and so on [21][22][23]. The rational reasons for selection of CP are as follows: (1) its anti-tumor activity has been extensively examined, particularly in clinical trials [24][25][26], and (2) the molecular mechanisms and pathways involved in CP resistance/sensitivity have been explored [27][28][29]. Consequently, it has been possible to implicate the process of EMT in drug resistance and directing further studies towards targeting EMT in suppressing resistance developed against CP treatment.…”

Gastric Cancer: Advances in Carcinogenesis Research and New Therapeutic Strategies

“…miR-192-5p and miR-9-5p are highly decreased in GC tissues compared to non-tumorous gastric tissues and can thus be candidate for GC diagnosis [ 113 ]. Moreover, miR-9-5p and a combined miRNA group (miR-9-5p + miR-9-3p + miR-433-3p) were found to distinguish chemo-resistant GC patients from chemo-sensitive ones [ 114 ], confirming the interest of miRNA as novel non-invasive diagnostic tool in GC.…”

Microbiome–miRNA interactions in the progress from undifferentiated arthritis to rheumatoid arthritis: evidence, hypotheses, and opportunities

“…Because of the stability, non-invasiveness, and sensitivity of miRNAs, the abnormal expression of miRNAs might be useful for disease diagnosis [63][64][65]. The serum levels of miR-16-5p, miR-23-3p, miR125b-5p, miR-126-3p, miRN-146α-5p, and miR-223-3p in RA patients were identified as potential novel biomarkers for predicting and monitoring therapy outcomes to anti-TNFα/DMARD combination therapies [66].…”