Gastric cancer most commonly occurs in East Asia, and China accounts for more than half the of world's gastric cancer burden. Despite the efficacy of chemotherapy for patients, this treatment leads to significant patient inconvenience, toxicity and cost. The present study aimed to assess a non-toxic agent, glabridin, as a future chemotherapeutic approach for treating gastric cancer. Using cell proliferation, apoptosis, invasion, and colony formation assays, it was determined that glabridin alone, or in combination with 5-fluorouracil (5-FU), inhibited MKN-45 cell proliferation and invasion, and increased apoptosis. These effects were accompanied by downregulation of p16, E-cadherin and apoptosis regulator Bcl-2 protein, and upregulation of N-cadherin, apoptosis regulator BAX and caspases 3, 8 and 9. The results demonstrated that glabridin may inhibit the malignant proliferation of the human gastric cancer MKN-45 cell line and enhance the efficiency of 5-FU. The data indicate that the p16, and potentially the p16/cyclin-dependent kinase 4/cyclin D1 pathway, may be a novel target for gastric cancer therapy.
IntroductionCircular RNAs (CircRNAs), an emerging non-coding RNA, have been demonstrated to be involved in tumorigenesis, metastasis, and cancer progression, and could represent novel potential biomarkers for diagnosing oral squamous cell carcinoma (OSCC). However, no meta-analysis has investigated the diagnostic role of circRNAs in OSCC. Hence, to investigate whether circRNAs could serve as specific biomarkers for OSCC, the present systematic review and meta-analysis evaluated the diagnostic efficiency of circRNAs in patients with OSCC.Materials and MethodsA thorough search of online databases (Pubmed, Web of Science, Embase, and the Cochrane Library) was conducted to collect relevant studies up to March 30th, 2021. All eligible studies were case-control studies. The quality of each study was evaluated by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. STATA (version 15.1) and Review Manager (version 5.4) were employed to conduct the meta-analysis, and the PRISMA statement was adopted in this study.ResultsA total of 16 studies were included in the meta-analysis, with five studies on upregulated circRNAs, and 11 on downregulated circRNAs. The enrolled studies that met our eligibility criteria all derived from China. The pooled sensitivity (SEN), specificity (SPE), diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and the area under receiver operating characteristics curve (AUC) with the 95% confidence intervals (95% CIs) were 0.74 (0.69–0.79), 0.79 (0.73–0.84), 10.74 (7.81–14.77), 3.50 (2.78–4.45), 0.33 (0.27–0.39) and 0.83 (0.79–0.86), respectively. The subgroup analysis demonstrated that serum, plasma, and saliva specimens had a better diagnostic performance than tissue samples, with a high value of sensitivity, specificity, DOR, and AUC values. The results also showed that the subgroups of upregulated circRNAs and a sample size of ≥100 manifested higher specificity, DOR, and AUC for cancer detection than downregulated circRNAs and a sample size of < 100.ConclusionsA strong association was demonstrated between the dysregulated expression of circRNAs and the diagnosis of OSCC. Hence, circRNAs have the potential to function as promising biomarkers and therapeutic targets for OSCC.Systematic Review RegistrationPROSPERO, number CRD42021256857.
This systematic review was aimed to comprehensively evaluate the clinicopathological and prognostic value of dysregulated expression of circRNAs in OSCC. The research was carried out by searching mainstream electronic databases including PubMed, Embase, Web of Science, Scopus, LILACS, and Cochrane Library to collect relevant studies on prognostic role of circRNAs in OSCC. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between circRNAs expression, overall survival (OS), disease/recurrence/progression survival (DFS/RFS/PFS), and clinical parameters. This research included 1813 patients from 26 selected articles. The pooled HR values (95% CIs) in OS were 2.38 (1.92–2.93) for oncogenic circRNAs and 0.43 (0.28–0.66) for tumor‐suppressor circRNAs, respectively, in DFS/RFS/PFS were 2.34 (1.73–3.17). The meta‐analysis on clinicopathology features showed higher level of oncogenic circRNAs is related to advanced TNM stage, tumor stage, worse histological differentiation, positive lymph node and distant metastasis, while enforced expression of tumor‐suppressor circRNAs is related to inferior TNM stage, tumor stage and lymphatic metastasis. In conclusion, our meta‐analysis implies that circRNAs may be candidate biomarkers for the prognosis and clinicopathology of OSCC.
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