No abstract

Tumour-infiltrating immune cells have been indicated to play an important role in prognosis prediction and therapy sensitivity for breast cancer. In recent years, estimating the abundance of immune cells based on tumour transcriptome data has provided a novel way to analyse the clinical significance of various immune cell subsets. This study integrated breast cancer tissue transcriptome datasets from the Gene Expression Omnibus (GEO), the Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohorts. A novel breast cancer immunotyping and a new prognostic model based on tumour-infiltrating immune cell subsets have been established, aiming to provide new clues regarding prognostic prediction and precision therapy for breast cancer. The key differentially expressed gene between different breast cancer immunotypes has also been identified. We performed unsupervised clustering analysis and construct a novel immunotyping which could classify breast cancer cases into immunotype A (B_cell high NK high CD8 + _T high CD4 + _memory_T_activated high γδT low Mast_cell_activated low Neutrophil low ) and immunotype B (B_cell low NK low CD8 + _T low CD4 + _memory_T_activated low γδT high Mast_cell_activated high Neutrophil high ) in luminal B, HER2-enriched and basal-like subtypes. The 5-year (85.7% vs. 73.4%) and 10-year OS (75.60% vs. 61.73%) of immunotype A population were significantly higher than those of immunotype B. A novel tumour-infiltrating immune cell-based prognostic model had also been established and the result immunorisk score (IRS) could serve as a new prognostic factor for luminal B, HER2-enriched and basal-like breast cancer. The higher IRS was, the worse prognosis was. We further screened the differentially expressed genes between immunotype A and B and identified a novel breast cancer immune-related gene, prostaglandin D2 synthase (PTGDS) and higher PTGDS mRNA expression level was positively correlated with earlier TNM stage. Immune-related signaling pathways analysis and immune cell subsets correlation analysis revealed that PTGDS expression was related with abundance of B cells, CD4 + T cells and CD8 + T cells, which was finally validated by immunohistochemical and immunofluorescence staining. We established a novel immunotyping and a tumour-infiltrating immune cell-based prognostic prediction model in luminal B, HER2-enriched and basal-like breast cancer by analyzing the prognostic significance of multiple immune cell subsets. A novel breast cancer immune signature gene PTDGS was discovered, which might serve as a protective prognostic factor and play an important role in breast cancer development and lymphocyte-related immune response.

Human discs large‐associated protein 5 (DLGAP5), a microtubule‐associated protein, has been reported to be upregulated in several tumors. However, the role of DLGAP5 in endometrial cancer (EC) progression and the related underlying mechanism were still unknown. A bioinformatics analysis was performed to analyze the expression and prognostic significance of DLGAP5 in EC tissues using TCGA, CPTAC, Human Protein Atlas, and GSE63678 databases, UALCAN web tool, and the Kaplan–Meier plotter. Effects of DLGAP on EC cell malignant properties were evaluated by CCK‐8, flow cytometry analysis, TUNEL assay, caspase‐3 activity assay, and Transwell invasion assay. The expression of DLGAP5, Wnt3, c‐Myc, Ki67, and cleaved caspase‐3 was detected by western blot analysis. DLGAP5 was highly expressed and correlated with poor prognosis in EC patients. DLGAP5 knockdown inhibited proliferation and invasion, triggered apoptosis, and increased caspase‐3 activity in EC cells. Additionally, DLGAP5 knockdown inactivated the Wnt/β‐catenin signaling pathway in EC cells. Moreover, β‐catenin overexpression abolished the effects of DLGAP5 knockdown on the malignant phenotypes of EC cells. DLGAP5 silencing suppressed the malignant properties in EC cells by inactivating the Wnt/β‐catenin pathway.

Background:For children with catastrophic epilepsy, vagus nerve stimulation has been demonstrated as a palliative treatment for those with surgical contraindication. The purpose of our study was to assess the efficacy on seizures, to assess the neuropsychological efficacy of vagus nerve stimulation in children. Methods:Our study reviewed files of 56 children treated with vagus nerve stimulation between May, 2008 and December, 2013 in our center. Data was collected from baseline to 12, 24 months of follow-up, including seizure frequency, seizure duration, seizure severity and neuropsychological outcomes. Results:In the population of these 56 children, vagus nerve stimulation significantly reduced seizure frequency, duration and severity. The response rates (reduction >50%) were 46.4%, 57.2% at 12 months, 24 months. Furthermore, VNS also significantly achieved improvement of neuropsychological outcomes, particularly the language function of the children under 6 years. Conclusion:The children with catastrophic epilepsy, especially those under 6 years, could benefit from vagus nerve stimulation by reducing seizure burden and improving neuropsychological development.

Background: Whether or not EGFR mutation status detected by ddPCR in plasma predicts the effect of icotinib on patients with advanced lung adenocarcinoma was determined.Methods: Plasma and matched tissue specimens from patients with advanced lung adenocarcinoma were collected prior to icotinib treatment. The ARMS method was used to detect EGFR mutation status in DNA extracted from tissue specimens, while the EGFR mutation status in ctDNA extracted from plasma specimens was determined by ddPCR. The therapeutic effects of icotinib were compared between patients with EGFRactivating mutations detected by ddPCR in ctDNA and ARMS in tissue DNA.Results: EGFR mutation status was detected in 96 tissue and 100 plasma specimens. The sensitivity and positive predictive value of 19del detected in ctDNA by ddPCR was 70.97% (22/31) and 44.90% (22/49), respectively. The positive predictive value was 84.62% (22/26) and the sensitivity was 53.66% (22/41) for the L858R mutation. For the common sensitive EGFR mutations, ddPCR had a positive predictive value of 77.19% (44/57) and a sensitivity of 48.89% (44/90). Patients with sensitive EGFR mutations in ctDNA had objective response and disease control rates (DCR) similar to patients who had sensitive EGFR mutations in tissues detected by ARMS when treated with icotinib (57.14% vs. 51.51% and 92.86% vs. 90.91%, respectively).Conclusions: Patients with sensitive EGFR mutations in plasma specimens detected with ddPCR had a higher ORR and DCR compared with patients with sensitive EGFR mutations in tissue detected with the ARMS method.