Abstract
Background: The morbidity and mortality of gastric cancer (GC) remain high worldwide. With the advent of the Human Genome Sequencing Project, circular RNAs (circRNAs) have attracted widespread attention in cancer research due to their stable ring structure. Our aim was to identify differentially expressed circRNAs in GC and explore their potential roles in GC diagnosis, treatment, and prognostic prediction.Methods: Large-scale gene screening was performed in three pairs of GC tissues and adjacent noncancerous tissues using high-throughput sequencing. The expression of hsa_circ_0001821 was detected in 80 pairs of tissue samples by quantitative real-time PCR (qRT-PCR). Stability of the ring structure of hsa_circ_0001821 RNA was verified by exonuclease digestion assay, and its diagnostic value was evaluated by receiver operating characteristic (ROC) analysis. In addition, the location of hsa_circ_0001821 in GC cells was detected by nucleoplasm separation assay.Results: A total of 25,303 circRNAs were identified, among which 2,007 circRNAs were differentially expressed (fold change > 2.0, P < 0.05). Further validation disclosed that hsa_circ_0001821 was significantly downregulated in the 80 pairs of GC tissues and 30 whole-blood specimens obtained from the GC patients. The specificity of hsa_circ_0001821 in GC was higher than that in other solid tumors. In addition, hsa_circ_0001821 was relatively stable after RNA exonuclease digestion. Clinicopathological parameter analysis showed that hsa_circ_0001821 was negatively correlated with tumor depth (r = −0.255, P = 0.022) and lymph node metastasis (r = −0.235, P = 0.036). Area under the curve (AUC) analysis showed that the diagnostic efficiency of circulating hsa_circ_0001821 in distinguishing GC patients was higher than that in GC tissues (0.872, 95%CI: 0.767–0.977 vs. 0.792, 95%CI: 0.723–0.861). Combined use of circulating hsa_circ_0001821 with the existing tumor markers yielded the largest AUC of 0.933. Finally, hsa_circ_0001821 was demonstrated to mainly locate in the cytoplasm, implying that it played a potential regulatory role in GC at the posttranscriptional level.Conclusion: Hsa_circ_0001821 may prove to be a new and promising potential biomarker for GC diagnosis.
Highlights
Gastric cancer (GC) remains one of the most common malignant tumors worldwide
Further validation disclosed that hsa_circ_0001821 was significantly downregulated in the 80 pairs of GC tissues and 30 whole-blood specimens obtained from the GC patients
Area under the curve (AUC) analysis showed that the diagnostic efficiency of circulating hsa_circ_0001821 in distinguishing GC patients was higher than that in GC tissues (0.872, 95%CI: 0.767–0.977 vs. 0.792, 95%CI: 0.723–0.861)
Summary
Gastric cancer (GC) remains one of the most common malignant tumors worldwide. Approximately 934,000 new cases of GC are diagnosed every year, among which about 43% (400,000) occur in China with morbidity and mortality rates about twofold higher than the world average (Cheng et al, 2016; Miller et al, 2016). Patients with advanced GC may have a 50–70% chance of recurrence after surgery, and their 5-year survival rate is often less than 30% (Sun and Yan, 2016). The early detection rate of GC is less than 10%, and the disease is usually diagnosed in the advanced stage or when metastasis has already occurred. The morbidity and mortality of gastric cancer (GC) remain high worldwide. Our aim was to identify differentially expressed circRNAs in GC and explore their potential roles in GC diagnosis, treatment, and prognostic prediction
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