This study was conducted in order to analyze the prognostic effects of epidermal growth factor receptor (EGFR) and CDKN2A alterations and determine the prognostic significance of EGFR and CDKN2A ...alterations on regulated genes in patients with glioblastoma (GBM) or lower grade glioma (LGG).
The alteration frequencies of EGFR and CDKN2A across 32 tumor types were derived from cBioPortal based on The Cancer Genome Atlas (TCGA) datasets. The Kaplan-Meier analysis was used to determine the prognostic significance of EGFR and CDKN2A alterations. EGFR and CDKN2A alterations on regulated expression signatures were identified from RNA-seq data in the TCGA GBM datasets. The prognostic significance of EGFR and CDKN2A alterations on regulated genes in patients with glioma was determined using the TCGA and the Chinese Glioma Genome Atlas (CGGA) datasets.
Compared with the other 31 tumor types, EGFR amplification and CDKN2A deletion particularly occurred in patients with GBM. GBM patients with EGFR amplification or CDKN2A deletion demonstrated poor prognosis. Statistical analysis showed the coexistence of EGFR alteration and CDKN2A deletion in GBM patients. We identified 864 genes which were commonly regulated by EGFR amplification and CDKN2A deletion, and those genes were highly expressed in brain tissues and associated with the cell cycle, EBRR2, and MAPK signaling pathways.
(
) was upregulated in GBM patients with EGFR amplification or CDKN2A alteration. Higher expression levels of
were associated with worse prognosis in patients with GBM in both TCGA and CGGA datasets. Moreover, the expression levels of
were higher in patients with a mesenchymal subtype of GBM. Statistical analysis also showed that the coexistence of EGFR alteration and CDKN2A deletion was significant in patients with LGG.
was upregulated in LGG patients with EGFR amplification or CDKN2A alteration. Furthermore, higher expression levels of
were associated with worse prognosis in patients with LGG in both TCGA and CGGA datasets. The expression levels of
were higher in patients with an astrocytoma subtype of LGG. Finally, the coexistence and unfavorable prognostic effects of EGFR amplification and CDKN2A alteration were validated using the Memorial Sloan Kettering Cancer Center (MSKCC) glioma datasets.
EGFR amplification and CDKN2A deletion of the regulated gene
have significant prognostic effects in patients with GBM or LGG.
Abstract
Background
Genetic 1p deletion is reported in 30% of all neuroblastoma and is associated with the unfavorable prognosis of neuroblastoma. The expressions and prognosis of 1p candidate genes ...in neuroblastoma are unclear.
Methods
Public neuroblastoma cohorts were obtained for secondary analysis. The prognosis of 1p candidate genes in neuroblastoma was determined using Kaplan-Meier and cox regression analysis. The prediction of the nomogram model was determined using timeROC.
Results
First, we confirmed the bad prognosis of 1p deletion in neuroblastoma. Moreover, zinc finger protein 436 (ZNF436) located at 1p36 region was down-regulated in 1p deleted neuroblastoma and higher ZNF436 expression was associated with the longer event free survival and overall survival of neuroblastoma. The expression levels of ZNF436 were lower in neuroblastoma patients with MYCN amplification or age at diagnosis ≥ 18months, or with stage 4 neuroblastoma. ZNF436 had robust predictive values of MYCN amplification and overall survival of neuroblastoma. Furthermore, the prognostic significance of ZNF436 in neuroblastoma was independent of MYCN amplification and age of diagnosis. Combinations of ZNF436 with MYCN amplification or age of diagnosis achieved better prognosis. At last, we constructed a nomogram risk model based on age, MYCN amplification and ZNF436. The nomogram model could predict the overall survival of neuroblastoma with high specificity and sensitivity.
Conclusions
Chromosome 1p36 candidate gene ZNF436 was a prognostic maker of neuroblastoma.
Electric vehicle (EV) has been popularized and promoted on a large scale because of its clean and efficient features. Charging this increasing number of EVs is expected to have an impact on the ...electricity grid and traffic network. Therefore, it is necessary to model and forecast the EV charging demand. Most of the existing researches have not utilized real-world traffic data to analyze the EV charging demand. Few researches have considered and analyzed the characteristics of space-time transfer of charging load in urban functional areas. As an emerging mode of transportation, however, online ride-hailing trip data provide an ideal source for analyzing traffic planning and operation. On the basis of this, a charging demand forecasting model of EVs based on a data-driven approach was presented in this paper. In this methodology, it is firstly assumed that residents' transportation trip demand is not restricted by vehicle categories(electric or fuel vehicles). The original trip trajectory data of Didi online ride-hailing were conducted to model via data mining and fusion. And the process of data analysis included region-scope selection, spatial grid modeling, trajectory data mapping, retrieval data identification and urban functional area clustering as well as traffic network modeling. Through modeling and processing, the following regenerative feature data were obtained: functional regional division (i.e., residential areas, industrial areas, commercial areas, and public service areas), trip rule distribution (i.e., temporal distribution and spatial distribution on weekdays, weekends and holidays) and actual driving path (i.e., driving path with the shortest distance or with the minimum time-consuming). And then, considering the movable load feature of EVs, vehicles were subdivided into three kinds such as private vehicles, taxis and other public vehicles, and the single EV model with driving and charging characteristic parameters was established. Furthermore, the regeneration data obtained from modeling and analysis along with the determined single EV model were supported as data sources and model for the charging demand forecast architecture. At last, the actual urban traffic network in Nanjing, China was selected as an example to design the path planning experiments and charging demand load experiments in different scenarios. The results demonstrate that this proposed model is able to realistically simulate the actual dynamic driving process of EVs, and effectively predict the spatial-temporal distribution characteristics and load transfer trends of charging demands in different date type as well as different functional areas. The model also lays a theoretical foundation for the subsequent research on investment and construction of charging facilities, as well as charging control and charging guidance of EVs.
This paper proposed an innovative electrochemical method for copper recovery from spent sulfide slag (Na2S-FeS-Cu2S), generated during copper removal from iron-based melts. It aims to reduce the high ...decopperization agents' consumption caused by low copper distribution ratio during the copper removal process, address the cost issues by recycle of slag and recovery of copper, and expand the application potential of the emerging copper removal method using the sulfide slag systems. The feasibility of electro-recovery of copper is verified by cyclic voltammetry tests and potentiostatic electrolysis experiments. The results show that in the Na2S-FeS-Cu2S melt, although copper cannot be reduced alone without reducing iron, rough separation can be achieved by controlling the temperature. The current efficiency of Cu+ reduction in the molten sulfide is about 9.1% due to electronic conduction in the sulfide melt, which needs further improvement. The slag treated by the innovative electrochemical process can be reused, as the XRD results show that it has a similar composition to the primary slag unused.
Neuroblastoma patients with MYCN amplification are associated with poor prognosis. However, the prognostic relevance of MYCN associated genes in neuroblastoma is unclear.
The expression profiles of ...MYCN associated genes were identified from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) datasets. Enriched transcription factors and signaling pathways were determined using gene set enrichment analysis (GSEA). Kaplan-Meier plotter was used to identify the prognostic relevance of MYCN associated genes. Multivariate cox regression and Spearman's correlation were used to determine the correlation coefficients of MYCN associated genes.
In TARGET and GSE85047 datasets, neuroblastoma patients with MYCN amplification were associated with worse prognosis. Transcription factor MYC was positively associated with MYCN amplification in GSEA assay. We identified 13 MYC target genes which were increased in neuroblastoma patients with MYCN amplification in TARGET, GSE19274 and GSE85047 datasets. Moreover, six out of the 13 MYC target genes ARMC6, DCTPP1, EIF4G1, ELOVL6, FBL and PRMT1 were associated with adverse prognosis in TARGET and GSE85047 datasets. Transcription factor E2F1 was up-regulated by MYCN amplification and associated with the poor prognosis of neuroblastoma. Furthermore, RPS19 in ribosome signaling pathway was also associated with MYCN amplification and correlated with the poor prognosis of neuroblastoma. At last, we showed that most of MYCN target genes were correlated with each other. However, EIF4G1 was an independent prognostic marker. And the prognostic effects of the combination of MYCN amplification and EIF4G1 expression were more significant than MYCN or EIF4G1 alone.
MYCN target genes ARMC6, DCTPP1, EIF4G1, ELOVL6, FBL, PRMT1, E2F1 and RPS19 had significant prognostic effects in pediatric neuroblastoma. And neuroblastoma patients without MYCN amplification and low EIF4G1 expression had best prognosis.
Mutagenic nucleoside analogues can be used to isolate RNA virus high-fidelity RNA-dependent RNA polymerase (RdRp) variants, the majority of which are attenuated in vivo. However, attenuated ...foot-and-mouth disease virus (FMDV) high-fidelity RdRp variants have not been isolated, and the correlations between RdRp fidelity and virulence remain unclear. Here, the mutagen ribavirin was used to select a ribavirin-resistant population of FMDV, and 4 amino acid substitutions (D5N, A38V, M194I, and M296V) were identified in the RdRp-coding region of the population. Through single or combined mutagenesis using a reverse genetics system, we generated direct experimental evidence that the rescued D5N, A38V, and DAMM mutants but not the M194I and M296V mutants are high-fidelity RdRp variants. Mutagen resistance assays revealed that the higher replication fidelity was associated with higher-level resistance to ribavirin. In addition, significantly attenuated fitness and virulence phenotypes were observed for the D5N, A38V, and DAMM mutants. Based on a systematic quantitative analysis of fidelity and virulence, we concluded that higher replication fidelity is associated with a more attenuated virus. These data suggest that the resulting restricted quasispecies diversity compromises the adaptability and virulence of an RNA virus population. The modulation of replication fidelity to attenuate virulence may represent a general strategy for the rational design of new types of live, attenuated vaccine strains.
The ribavirin-isolated poliovirus (PV) RdRp G64S variant, the polymerases of which were of high replication fidelity, was attenuated in vivo. It has been proposed (M. Vignuzzi, E. Wendt, and R. Andino, Nat. Med. 14:154-161, http://dx.doi.org/10.1038/nm1726) that modulation of replication fidelity is a promising approach for engineering attenuated virus vaccines. The subsequently mutagen-isolated RdRp variants also expressed the high-fidelity polymerase, but not all of them were attenuated. Few studies have shown the exact correlation between fidelity and virulence. The present study investigates the effect of restricted quasispecies diversity on viral virulence via several attenuated FMDV high-fidelity RdRp variants. Our findings may aid in the rational design of a new type of vaccine strain.
Programmed cell death protein 1(PD-1) blocking antibodies have been used to enhance immunity in solid tumors and achieve durable clinical responses with an acceptable safety profile in multiple types ...of cancer. However, only a subset of patients could benefit from PD-1 blockade therapy. Prognostic information including PD-1 ligand (PD-L1) expression, IFN-γ expression signature, tumor mutational burden, and microsatellite instability (MSI) have been evaluated for patients who are selected to receive immune checkpoint therapeutic treatment. Yet the relationship of those biomarkers in determining immune checkpoint therapy is largely unknown.
Immune-profiles of MSI subtype colon cancer were identified from integrating published MSI associated gene expression data. The enriched pathways and transcription factors were analyzed by GSEA assay. The infiltrations of immune cell types into MSI subtype colon cancer tissues were determined by CIBESORT assay.
In the MSI subtype colon cancer patients, PD-L1, IFN-γ and IFN-γ associated genes are highly expressed. And all those genes are favorable effects in colon cancer progress. In addition, we find that Wnt-β-catenin and TGFβ signaling pathways which are two important factors inhibiting PD-1 checkpoint blockade therapy are negatively related with MSI status. We also identify that the immune-profiles in MSI subtype colon cancer are contributed by M1 macrophage infiltration in the tumor environment.
Our results provide the detailed underlying mechanisms of MSI subtype cancer patients are sensitive to PD-1 checkpoint blockade.
Background
A subgroup of glioma carry genetic 4q12 amplification including platelet derived growth factor receptor α (PDGFRA) and insulin like growth factor binding protein 7 (IGFBP7). However, the ...prognosis of PDGFRA and IGFBP7 in glioma is unclear.
Methods
The prognosis of PDGFRA and IGFBP7 was determined using cox regression and Kaplan–Meier survival analysis. Pathways associated with IGFBP7 were analyzed through gene set enrichment analysis (GSEA). Immune profiling of glioma was determined using “ESTIMATE” and “TIMER” database.
Results
PDGFRA amplification or expression was not correlated with the outcomes of glioblastoma (GBM). IGFBP7 but not PDGFRA was over‐expressed in GBM. IGFBP7 over‐expression was correlated with the unfavorable outcomes of GBM. In lower grade glioma (LGG), PDGFRA over‐expression was not correlated with the unfavorable prognosis of LGG, while, IGFBP7 was a prognostic biomarker of LGG. LGG patients with IGFBP7 lower expressions had prolonged clinical overall survival. Combination of IDH mutation, LGG grade and IGFBP7 achieved even better prognostic effects in LGG. Moreover, IGFBP7 was over‐expressed in glioma patients with wild type IDH or with high grades. IGFBP7 over‐expression was correlated with the unfavorable outcomes of glioma. Furthermore, IGFBP7 was hypo‐methylated in GBM or LGG patients without IDH mutations. IGFBP7 hyper‐methylation was correlated with the lower overall survival of GBM or LGG. LGG patients with wild type IDH and with IGFBP7 hypo‐methylation demonstrated even worse prognosis. IGFBP7 was associated with multiple immune‐related signaling pathways in GBM or LGG. The stromal score, immune score and the infiltrations of immune cells were also correlated with IGFBP7 and the prognosis of LGG.
Conclusions
IGFBP7 but not PDGFRA served an ideal prognostic marker and therapeutic target of glioma.
PDGFRA and IGFBP7 were co‐amplifying in glioma. IGFBP7 but not PDGFRA served an ideal prognostic marker and therapeutic target of glioma. IGFBP7 was associated with the glioma immune infiltrations.
Plenoptic cameras have received a wide range of research interest because it can record the 4D plenoptic function or radiance including the radiation power and ray direction. One of its important ...applications is digital refocusing, which can obtain 2D images focused at different depths. To achieve digital refocusing in a wide range, a large depth of field (DOF) is needed, but there are fundamental optical limitations to this. In this paper, we proposed a plenoptic camera with an extended DOF by integrating a main lens, a tunable multi-focus liquid-crystal microlens array (TMF-LCMLA), and a complementary metal oxide semiconductor (CMOS) sensor together. The TMF-LCMLA was fabricated by traditional photolithography and standard microelectronic techniques, and its optical characteristics including interference patterns, focal lengths, and point spread functions (PSFs) were experimentally analyzed. Experiments demonstrated that the proposed plenoptic camera has a wider range of digital refocusing compared to the plenoptic camera based on a conventional liquid-crystal microlens array (LCMLA) with only one corresponding focal length at a certain voltage, which is equivalent to the extension of DOF. In addition, it also has a 2D/3D switchable function, which is not available with conventional plenoptic cameras.
MYCN amplification and age are two critical prognostic factors of pediatric neuroblastoma. Previously, we had revealed the prognosis of MYCN target genes. However, the prognostic effects of age ...related genes in neuroblastoma are unclear.
The prognostic significance of age and MYCN amplification was determined through multivariate cox regression and Kaplan-Meier survival analysis. Genes differentially expressed in MYCN non-amplified younger neuroblastoma patients were identified using Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) datasets. The prognostic effects of age related genes ALCAM, CACNA2D3, DST, EPB41L4A and KIF1B in pediatric neuroblastoma patients were determined by Kaplan-Meier survival.
In a pediatric pan-cancer analysis, age was associated with the overall survival of pediatric B-lineage acute lymphoblastic leukemia, neuroblastoma and wilms tumor in TARGET dataset. Moreover, the prognostic effects of age in neuroblastoma were validated using two independent neuroblastoma cohorts. Furthermore, age and MYCN amplification were independent prognostic factors in pediatric neuroblastoma. Compared with MYCN non-amplified older neuroblastoma patients, MYCN non-amplified younger neuroblastoma patients had better clinical outcomes. ALCAM, CACNA2D3, DST, EPB41L4A and KIF1B were highly expressed in MYCN non-amplified younger neuroblastoma patients. And the higher expression levels of ALCAM, CACNA2D3, DST, EPB41L4A or KIF1B were associated with better prognosis of MYCN non-amplified neuroblastoma patients. DST was an independent prognostic factor in MYCN non-amplified neuroblastoma patients and MYCN non-amplified neuroblastoma younger patients with higher DST expression levels had the best clinical overall survival.
Age related gene DST was an independent prognostic factor in MYCN non-amplified neuroblastoma. MYCN non-amplified younger neuroblastoma patients with higher DST expression levels had the best clinical overall survival.
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