Circ_0078607 increases platinum drug sensitivity via miR-196b-5p/GAS7 axis in ovarian cancer.

Platinum-based chemotherapy is one of the predominant strategies for treating ovarian cancer (OC), however, platinum resistance greatly influences the therapeutic effect. Circular RNAs (circRNAs) have been found to participate in the pathogenesis of platinum resistance. Our aim was to explore the involvement of circ_0078607 in OC cell cisplatin (DDP) resistance and its potential mechanisms. Circ_0078607, miR-196b-5p, and growth arrest-specific 7 (GAS7) levels were assessed by qPCR. Circ_0078607 stability was assessed by ribonuclease R digestion and actinomycin D treatment. Cell viability of various conic of DDP treatment was measured by CCK-8. The cell proliferation was determined by CCK-8 and colony formation assay. Western blotting was performed for determining GAS7, ABCB1, CyclinD1 and Bcl-2 protein levels. The direct binding between miR-196b-5p and circ_0078607 or GAS7 was validated by dual-luciferase reporter and RIP assay. DDP resistance in vivo was evaluated in nude mice. Immunohistochemistry staining for detecting Ki67 expression in xenograft tumours. Circ_0078607 and GAS7 was down-regulated, but miR-196b-5p was up-regulated in OC samples and DDP-resistant cells. Overexpression of circ_0078607 inhibited DDP resistance, cell growth and induced apoptosis in DDP-resistant OC cells. Mechanistically, circ_0078607 sequestered miR-196b-5p to up-regulate GAS7. MiR-196b-5p mimics reversed circ_0078607 or GAS7 overexpression-mediated enhanced sensitivity. Finally, circ_0078607 improved the sensitivity of DDP in vivo. Circ_0078607 attenuates DDP resistance via miR-196b-5p/GAS7 axis, which highlights the therapeutic potential of circ_0078607 to counter DDP resistance in OC.

CCR7 Has Potential to Be a Prognosis Marker for Cervical Squamous Cell Carcinoma and an Index for Tumor Microenvironment Change.

The tumor microenvironment (TME) has an essential role in the development of cervical squamous cell carcinoma (CSCC); however, the dynamic role of the stromal and immune cells is still unclear in TME. We downloaded data from The Cancer Genome Atlas (TCGA) database and applied ESTIMATE and CIBERSORT algorithms to measure the quantity of stromal and immune cells and the composition of tumor-infiltrating immune cell (TIC) in 253 CSCC cases. The protein-protein interaction (PPI) network and Cox regression analysis presented the differentially expressed genes (DEGs). Then, C-C chemokine receptor type 7 (CCR7) was screened out as a prognostic marker by the univariate Cox and intersection analysis of PPI. Further analysis showed a positive correlation between the expression of CCR7 and the survival of CSCC patients. The result of the Gene Set Enrichment Analysis (GSEA) of genes in the high CCR7 expression group displayed a predominant enrichment in immune-related pathways. An enrichment in metabolic activities was observed in the low CCR7 expression group. CIBERSORT analysis showed a positive correlation between Plasma cells, CD8+ T cells, and regulatory T cells and the CCR7 expression, suggesting that CCR7 might play a crucial role in maintaining the immunological dominance status for TME. Therefore, the expression level of CCR7 might help predict the survival of CSCC cases and be an index that the status of TME transitioned from immunological dominance to metabolic activation, which presented a new insight into the treatment of CSCC.

Prognostic Impact of Epidermal Growth Factor Receptor Overexpression in Patients with Cervical Cancer: A Meta-Analysis.

Clinical trials have provided conflicting results regarding whether epidermal growth factor receptor (EGFR) overexpression predicts poor survival in cervical cancer patients. In this study, we perform a meta-analysis of the association between EGFR expression and survival in cervical cancer patients. We searched clinical studies in the Medline, PubMed, Embase, and Web of Science databases. A total of 22 studies with 2,505 patients were included, and pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for each study. Heterogeneity was assessed using Higgins I2 to select a Mantel-Haenszel fixed effects model (I2 ≤50%) or a DerSimonian-Laird random effects model (I2 ≥50%). High EGFR levels predicted poor overall survival (OS) (HR: 1.40, 95% CI: 1.10-1.78) and disease-free survival (DFS) (HR: 1.84, 95% CI: 1.51-2.24). Stratified analyses showed that EGFR overexpression was significantly related to poor DFS in patients treated with chemoradiation or surgery. Moreover, the pooled odds ratios (ORs) revealed associations between EGFR expression and clinicopathological features, such as lymph node metastasis (OR: 1.72, 95% CI: 1.23-2.40) and tumor size ≥4 cm (OR: 1.64, 95% CI: 1.20-2.23). This meta-analysis demonstrates that EGFR overexpression is closely associated with reduced survival in patients with cervical cancer. These results may facilitate the individualized management of clinical decisions for anti-EGFR therapies in cervical cancer patients.