Construction of an immunogenic cell death-based risk score prognosis model in breast cancer

Immunogenic cell death (ICD) is a form of regulated cell death that elicits immune response. Common inducers of ICD include cancer chemotherapy and radiation therapy. A better understanding of ICD might contribute to modify the current regimens of anti-cancer therapy, especially immunotherapy. This study aimed to identify ICD-related prognostic gene signatures in breast cancer (BC). An ICD-based gene prognostic signature was developed using Lasso-cox regression and Kaplan-Meier survival analysis based on datasets acquired from the Cancer Genome Atlas and Gene Expression Omnibus. A nomogram model was developed to predict the prognosis of BC patients. Gene Set Enrichment Analysis (GESA) and Gene Set Variation Analysis (GSVA) were used to explore the differentially expressed signaling pathways in high and low-risk groups. CIBERSORT and ESTIMATE algorithms were performed to investigate the difference of immune status in tumor microenvironment of different risk groups. Six genes (CALR, CLEC9A, BAX, TLR4, CXCR3, and PIK3CA) were selected for construction and validation of the prognosis model of BC based on public data. GSEA and GSVA analysis found that immune-related gene sets were enriched in low-risk group. Moreover, immune cell infiltration analysis showed that the immune features of the high-risk group were characterized by higher infiltration of tumor-associated macrophages and a lower proportion of CD8+ T cells, suggesting an immune evasive tumor microenvironment. We constructed and validated an ICD-based gene signature for predicting prognosis of breast cancer patients. Our model provides a tool with good discrimination and calibration abilities to predict the prognosis of BC, especially triple-negative breast cancer (TNBC)

MiR-361-5p inhibits glycolytic metabolism, proliferation and invasion of breast cancer by targeting FGFR1 and MMP-1

Abstract Background MicroRNAs function as key regulators in various human cancers, including breast cancer (BC). MiR-361-5p has been proved to be a tumor suppressor in colorectal cancer and gastric cancer in our previous study. In this study, we aim to find out the function of miR-361-5p in breast cancer progression and elaborate the mechanism that miR-361-5p acts its function in breast cancer. Methods and results Here we reported that miR-361-5p was down-regulated in breast cancer tissue compared with normal breast tissue and the expression of miR-361-5p was positively associated with prognosis in BC patients. Functional studies showed that overexpression of miR-361-5p suppressed the proliferation, invasion and metastasis of breast cancer cells both in vivo and in vitro. Mechanistically, we found that miR-361-5p inhibited the proliferation of BC cells by suppressing glycolysis. FGFR1, a promoter of glycolysis-related enzyme, was identified as the target of miR-361-5p that promoted glycolysis and repressed oxidative phosphorylation. Furthermore, we demonstrated that miR-361-5p inhibited breast cancer cells invasion and metastasis by targeting MMP-1. An inverse expression pattern was also found between miR-361-5p and FGFR1 or MMP-1 in a cohort of 60 BC tissues. Conclusion Our results indicate that miR-361-5p inhibits breast cancer cells glycolysis and invasion by respectively repressing FGFR1 and MMP-1, suggesting that miR-361-5p and its targets may serve as therapeutic targets in breast cancer treatment

A Novel Ring-Gate AlGaN/GaN HEMT Device and Electrode Structure Optimization

In this paper, a novel ring-gate structure AlGaN/GaN HEMT device is proposed and fabricated successfully. When the gate-source spacing Lgs = 5 μm, gate-drain spacing Lgd = 7 μm, gate length Lg = 3 μm, the maximum drain current Idmax of this ring-gate AlGaN/GaN HEMT device improved by 161.8% comparing with the conventional structure device, the threshold voltage Vth increased by 66.7% from 1.65 V to 2.5 V. In order to further improve the performance of the device, a series of electrode structure optimization designs have been carried out. Firstly, the effect of source-drain electrode alloy type and etching depth under source-drain region on the transfer and output characteristics was investigated, we fabricated devices with two alloy electrodes of multi-layer Ti/Al/Ti/Al/Ti/Al/Ni/Au and single layer Ti/Al/Ni/Au, then perform groove etching under the source and drain electrodes, the etching depth is set to 10/20 nm, after analysis and calculation, it is found that among ring-gate and conventional-gate devices, the device with multi-layer electrodes and an etched depth of 10 nm performs best. Then, the influence of device size parameters on transfer and output characteristics was explored, devices with different Lg and Lgd were prepared, after testing it is found that with the increase of Lg, the Vth of the conventional-gate and ring-gate HEMT devices both showed a positive-shift trend, in conventional device Vth increased from 1.53 V to 1.7 V, and this value increased from 1.5 V to 2.5 V in ring-gate device; the saturation drain current decreases when Lg increasing, and the decrease of the ring-gate device is more obvious, from 51.28 mA at Lg = 3 μm to 24.48 mA at Lg = 6 μm; when Lds decreases, the Vth of the two structures doesn’t change significantly, but the output current increases with the reduction of Lds, among them, the Idmax of the conventional structure device at Lgd = 19 um is 79.07% lower than that at Lgd = 7 μm; the value of the ring-gate device is reduced by 113.7%. In addition, among all the above devices, the ring-gate devices all show better output characteristics and higher Vth than conventional devices

A Novel Ring-Gate AlGaN/GaN HEMT Device and Electrode Structure Optimization

In this paper, a novel ring-gate structure AlGaN/GaN HEMT device is proposed and fabricated successfully. When the gate-source spacing Lgs = 5 μm, gate-drain spacing Lgd = 7 μm, gate length Lg = 3 μm, the maximum drain current Idmax of this ring-gate AlGaN/GaN HEMT device improved by 161.8% comparing with the conventional structure device, the threshold voltage Vth increased by 66.7% from 1.65 V to 2.5 V. In order to further improve the performance of the device, a series of electrode structure optimization designs have been carried out. Firstly, the effect of source-drain electrode alloy type and etching depth under source-drain region on the transfer and output characteristics was investigated, we fabricated devices with two alloy electrodes of multi-layer Ti/Al/Ti/Al/Ti/Al/Ni/Au and single layer Ti/Al/Ni/Au, then perform groove etching under the source and drain electrodes, the etching depth is set to 10/20 nm, after analysis and calculation, it is found that among ring-gate and conventional-gate devices, the device with multi-layer electrodes and an etched depth of 10 nm performs best. Then, the influence of device size parameters on transfer and output characteristics was explored, devices with different Lg and Lgd were prepared, after testing it is found that with the increase of Lg, the Vth of the conventional-gate and ring-gate HEMT devices both showed a positive-shift trend, in conventional device Vth increased from 1.53 V to 1.7 V, and this value increased from 1.5 V to 2.5 V in ring-gate device; the saturation drain current decreases when Lg increasing, and the decrease of the ring-gate device is more obvious, from 51.28 mA at Lg = 3 μm to 24.48 mA at Lg = 6 μm; when Lds decreases, the Vth of the two structures doesn’t change significantly, but the output current increases with the reduction of Lds, among them, the Idmax of the conventional structure device at Lgd = 19 um is 79.07% lower than that at Lgd = 7 μm; the value of the ring-gate device is reduced by 113.7%. In addition, among all the above devices, the ring-gate devices all show better output characteristics and higher Vth than conventional devices