Gastric cancer (GC) is one of the most common malignancies worldwide. To the best of our knowledge, no biomarkers have been widely accepted for the early diagnosis and prognostic prediction of GC. This study aimed to identify potential novel prognostic biomarkers for GC. The dataset GSE29272, which originates from the public database Gene Expression Omnibus, was employed in the present study. The online tool GEO2R was used to calculate the differentially expressed genes (DEGs) in GSE29272 between tumour tissues and adjacent tissues. CytoHubba and MCODE plugins of Cytoscape software were used to obtain hub genes and modules of DEGs. The online tools Database for Annotation, Visualisation and Integrated Discovery and Search Tool for the Retrieval of Interacting Genes were employed to conduct Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis, and to construct protein-protein interaction networks. A total of 117 DEGs were extracted from GSE29272. In addition, 15 hub genes and seven modules were identified in the 117 DEGs. The enrichment analysis revealed that they were mainly enriched in GO biological process and cellular component domains, and the ‘ECM-receptor interaction’, ‘focal adhesion’, ‘metabolism of xenobiotics by cytochrome P450’ and ‘drug metabolism’ pathways. The hub genes asporin ( ASPN ), collagen type I α1 chain ( COL1A1 ), fibronectin 1 ( FN1 ), versican ( VCAN ) and mucin 5AC ( MUC5AC ) were demonstrated to have prognostic value for patients with GC. The ASPN and VCAN genes were significantly associated with overall survival and disease-free survival (log-rank P=0.025, 0.038, 0.0014 and 0.015, respectively). COL1A1 and FN1 were significantly associated with overall survival (log-rank P=0.013 and 0.05, respectively), and MUC5AC was significantly associated with disease-free survival (log-rank P=0.027). Results from the present study suggested that ASPN, COL1A1, FN1, VCAN and MUC5AC may represent novel prognostic biomarkers for GC.

Although significant progress has been made in the diagnosis and treatment of gastric cancer, the overall survival rate of the disease remains unchanged at approximately 20%‐25%. Thus, there is an urgent need for a better understanding of the molecular biology aspects of the disease in the hope of discovering novel diagnosis and treatment strategies. Recent years have witnessed decisive roles of aberrant cancer cell metabolism in the maintenance of malignant hallmarks of cancers, and cancer cell metabolism has been regarded as a novel target for the treatment of cancer. CDK2, a cell cycle‐dependent kinase that usually regulates cell cycle progression and the DNA damage response, is reported to be upregulated in many cancers. However, little is known about its role in cancer cell metabolism. In the present study, we showed that silencing CDK2 inhibited the aerobic glycolytic capacity of gastric cancer cell lines. Mechanism explorations showed that silencing CDK2 increased expression of the SIRT5 tumor suppressor. In addition, the physiological roles of SIRT5 in the regulation of proliferation and glycolysis were studied in gastric cancer cells. Taken together, the present study uncovered novel roles of the CDK2/SIRT5 axis in gastric cancer and suggests future studies concerning gastric cancer cell metabolism.

Due to a lack of effective methods for early diagnosis, the majority of patients with gastric cancer (GC) are diagnosed during the late stages of the disease, which are often accompanied by metastasis. For these patients, despite being considered an important therapeutic modality in the treatment of cancer, chemotherapy is usually not effective due to multidrug resistance (MDR). The expression levels of MDR/metastasis-associated genes are regulated by numerous microRNAs (miRNAs/miRs). The expression of miR-647 in GC tissues and SGC7901/VCR cell line (drug resistance to vincristine) was detected by qRT-PCR. The effect of overexpression of miR-647 on drug resistance was evaluated by measuring the half maximal inhibitory concentration (IC50) value of SGC-7901/VCR to vincristine and tumor growth in vivo. Moreover, drug-induced cell apoptosis and cell cycle were evaluated by flow cytometry, as well as the ability of cell migration and invasiveness detected by wound healing and transwell assay. Furthermore, underlying targets of miR-647 were predicted by TargetScan and MicroRNA; meanwhile, the expression of ANK2, FAK, MMP2, MMP12,CD44,SNAIL1 were observed by qRT-PCR and western blot analysis. The present study established that the expression levels of miR-647 were downregulated in GC tissues from patients with metastasis and in the vincristine-resistant SGC7901 (SGC-7901/VCR) GC cell line. The IC50 value for vincristine was significantly decreased, whereas the proportion of cells in G0/G1 phase and the drug-induced apoptotic rate were significantly increased following upregulation of miR-647. Furthermore, the results demonstrated that miR-647 overexpression led to decreased migration and invasion of SGC-7901/VCR cells. Overexpression of miR-647 was also demonstrated to sensitize tumors to chemotherapy in vivo. In addition, miR-647 overexpression was able to reduce the expression levels of ankyrin-B, focal adhesion kinase, matrix metalloproteinase (MMP)2, MMP12, cluster of differentiation 44 and snail family transcriptional repressor 1. In conclusion, these findings demonstrated that miR-647 may function as a novel target to ameliorate drug resistance and metastasis of GC cells.