Ovarian cancer (OV) is a considerable threat to the health of women due to its complex mechanisms and atypical symptoms. Various currently available treatments fail to substantially increase the survival rate of OV patients. The tumor microenvironment (TME) is gaining attention due to its role in tumorigenesis and tumor progression. This study mainly investigated the immune characteristics of OV by CIBERSORT and MCP-counter. We reclassified OV into four TME cell subtypes with different prognoses and evaluated the infiltration of the cells in each subtype. The immune risk of diverse subtypes was evaluated based on the immunoscore calculated by Cox regression analysis. The molecular mechanisms and hallmark pathways of the four subtypes were analyzed. The results indicate that the immune procancer cell subtype is associated with the worst prognosis, closely related to the high immune risk group, and characterized by low expression of checkpoints and MHC class I and II molecules, high expression of hypoxia-related genes, high enrichment of the EMT and hypoxia pathways, and low enrichment of the DNA repair and interferon α response pathways. This study contributes to the investigation of immune mechanisms and identifies more effective targets for immunotherapy of OV.

No abstract

Cisplatin (CDDP) chemoresistance seriously affects the prognosis and survival of patients with ovarian cancer (OC). Previous research has shown that circular RNA CDR1as is biologically associated with a large number of cancers. However, the molecular mechanism underlying the role of CDR1as in CDDP chemoresistance in OC remains unclear. Here, we investigated the mechanism of CDR1as in CDDP-resistant OC. First, we employed bioinformatics analysis and quantitative real-time PCR (qRT-PCR) to determine the expression of CDR1as and related RNAs in CDDP-sensitive and -resistant OC tissues and cells. Then, functional experiments were used to determine cell proliferation, invasion, migration, and apoptosis in CDDP chemoresistance and parent OC cells in vitro. The effect of CDR1as in CDDP chemoresistance OC progression was tested in nude mice in vivo. Moreover, dual-luciferase assays and RNA immunoprecipitation (RIP) were performed to confirm the interactions of CDR1as and related RNAs. Finally, we used Western blotting to determine protein expression levels. Our findings interpret the underlying mechanisms of the CDR1as/miR-1299/PPP1R12B axis and shed light on the clinical applications for CDDP-chemoresistant OC.

Background. Endometriosis is an inflammatory gynecological disease leading to deep pelvic pain, dyspareunia, and infertility. The pathophysiology of endometriosis is complex and depends on a variety of biological processes and pathways. Therefore, there is an urgent need to identify reliable biomarkers for early detection and accurate diagnosis to predict clinical outcomes and aid in the early intervention of endometriosis. We screened transcription factor- (TF-) immune-related gene (IRG) regulatory networks as potential biomarkers to reveal new molecular subgroups for the early diagnosis of endometriosis. Methods. To explore potential therapeutic targets for endometriosis, the Gene Expression Omnibus (GEO), Immunology Database and Analysis Portal (ImmPort), and TF databases were used to obtain data related to the recognition of differentially expressed genes (DEGs), differentially expressed IRGs (DEIRGs), and differentially expressed TFs (DETFs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the DETFs and DEIRGs. Then, DETFs and DEIRGs were further validated in the external datasets of GSE51981 and GSE1230103. Then, we used quantitative real-time polymerase chain reaction (qRT-PCR) to verify the hub genes. Simultaneously, the Pearson correlation analysis and protein-protein interaction (PPI) analyses were used to indicate the potential mechanisms of TF-IRGs at the molecular level and obtain hub IRGs. Finally, the receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value of the hub IRGs. Results. We screened a total of 94 DETFs and 121 DEIRGs in endometriosis. Most downregulated DETFs showed decreased expression in the endometria of moderate/severe endometriosis patients. The top-ranked upregulated DEIRGs were upregulated in the endometra of infertile women. Functional analysis showed that DETFs and DEIRGs may be involved in the biological behaviors and pathways of endometriosis. The TF-IRG PPI network was successfully constructed. Compared with the control group, high C3, VCAM1, ITGB2, and C3AR1 expression had statistical significance in endometriosis among the hub DEIRGs. They also showed higher sensitivity and specificity by ROC analysis for the diagnosis of endometriosis. Finally, compared with controls, C3 and VCAM1 were highly expressed in endometriosis tissue samples. In addition, they also showed high specificity and sensitivity for diagnosing endometriosis. Conclusion. Overall, we discovered the TF-IRG regulatory network and analyzed 4 hub IRGs that were closely related to endometriosis, which contributes to the diagnosis of endometriosis. Additionally, we verified that DETFs or DEIRGs were associated with the clinicopathological features of endometriosis, and external datasets also confirmed the hub IRGs. Finally, C3 and VCAM1 were highly expressed in endometriosis tissue samples compared with controls and may be potential biomarkers of endometriosis, which are helpful for the early diagnosis of endometriosis.

Purpose. The aim of the present prospective study was to evaluate the effect of titanium mesh and concentrated growth factor (CGF) membranes in reconstructing severe labial bone defects during immediate implantation of anterior maxillary tooth. Methods. Patients with severe defects presenting on the anterior labial bone plate of maxillary were enrolled in this study. During immediate implantation, the titanium mesh was used to maintain the space of bone graft, collagen membrane, and xenograft bone that were used to guide bone regeneration (GBR). Cone beam computed tomography (CBCT) was used to measure the height and the labial bone thickness around the implant at the time of the second stage surgery, 6 months, 1 year, and 2 years after restoration. The pink esthetic score (PES) was used to evaluate the esthetic outcomes after restoration. Results. 18 patients were enrolled in this study. The survival rate of implants was 100%, and no complication was observed, except for 1 case of titanium mesh exposure which did not affect osteogenesis. In the second stage of surgery, the labial bone was completely reconstructed, and the top of the implant was covered with a small amount of new bone. The thickness of the labial bone was 3.01 mm (±0.23), 2.96 mm (±0.21), 2.93 mm (±0.19), and 2.92 mm (±0.16) at the time of the second stage surgery, 6 months, 1 year, and 2 years after restoration, respectively. The height of the marginal bone around implants was above the top of implant at the time of the second stage surgery and then reduced 0.72 mm (±0.07), 0.91 mm (±0.08), and 0.90 mm (±0.07) at the time point of 6 months, 1 year, and 2 years after restoration, respectively. The changes of bone thickness and height were statistically significant within one year, but stable after one year. The PES values showed the same tendency. Conclusions. With the limitation of the present prospective study, the combination of titanium mesh and CGF membrane could provide space maintenance for bone augmentation of alveolar bone defects and improve the bone regeneration in patients with severe labial bone defect when immediate implant of anterior maxillary.