scholarly journals A panel of synapse assembly genes as a biomarker for Gliomas

2019 ◽  
Author(s):  
Xiangwen Ji ◽  
Hongwei Zhang ◽  
Qinghua Cui
Keyword(s):  
Gene Expression ◽  
Brain Metastasis ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Quantitative Method ◽  
Glioma Cells ◽  
Predictive Ability ◽  
Predictive Performance ◽  
Idh Mutation

AbstractGliomas are the most common primary brain cancers. In recent years, IDH mutation and 1p/19q codeletion have been suggested as biomarkers for the diagnosis, treatment and prognosis of gliomas. However, these biomarkers are only effective for a part of glioma patients and thus more biomarkers are still emergently needed. Recently, an electrochemical communication between normal neurons and glioma cells by neuro-glioma synapse has been reported. Moreover, it was discovered that breast-to-brain metastasis tumor cells have pseudo synapses with neurons and these synapses were indicated to promote tumor progression and metastasis. Based on the above observations, we first curated a panel of 66 SA genes and then proposed a metric, SA score, to quantify the synapseness for each sample of 12 glioma gene expression datasets from TCGA, CGGA, and GEO. Strikingly, SA score showed excellent predictive ability for the prognosis, diagnosis, and grading of gliomas. Moreover, being compared with the two established biomarkers, IDH mutation and 1p/19q codeletion, SA score was demonstrated independent and better predictive performance. In conclusion, this study revealed that SA genes contribute to glioma formation and development, and proposed a quantitative method, SA score, as an efficient biomarker for monitoring gliomas.

scholarly journals TMIC-58. THE CELLULAR AND MOLECULAR BASIS FOR MESENCHYMAL TRANSFORMATION IN GLIOMAS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi260-vi260
Author(s):  
Andrea Comba ◽  
Patrick J Dunn ◽  
Anna E Argento ◽  
Padma Kadiyala ◽  
Sebastien Motsch ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Tumor Cells ◽  
Smooth Muscle Actin ◽  
Glioma Cells ◽  
Time Lapse ◽  
Mesenchymal Cells ◽  
Genetically Engineered ◽  
Normal Brain ◽  
Mesenchymal Transformation ◽  
Glioma Progression

Abstract Mesenchymal gliomas are the most aggressive tumors that carry the worst prognosis. The origins of mesenchymal cells within brain tumors, remains poorly understood. They could originate either from invading mesenchymal cells, from perivascular smooth muscle actin+ cells, or from a mesenchymal transformation of tumor cells. Identifying the origin and function of mesenchymal cells within gliomas is essential as these cells contribute to increased glioma aggressiveness and tumor progression. In this study we used human biopsies and implantable and genetically engineered mouse models (GEMM) of GBM to study tumor mesenchymal transformation. GBM implantable models were used to analyze the molecular landscape by laser microdissection followed by RNA-Seq and bioinformatics analysis. Time lapse confocal imagining was implemented to analyze GBM cells dynamics. Our results indicate the existence of a complex intratumoral and peritumoral dynamic organization of glioma cells (i.e., Oncostreams). Multicellular structures of elongated cells compatible with mesenchymal differentiation. These structures play important roles in intratumoral movements, peritumoral invasion of normal brain, and overall glioma progression. We also show that oncostreams are molecularly distinct and display increased expression of mesenchymal genes such as Col1a1. Knocking down of Col1a1 in a GEMM of aggressive gliomas reduced tumor progression and significantly increased animal survival. Histological examination confirmed absence of Col1a1, and absence of morphologically identifiable oncostreams. Our results show that tumor cells, especially within oncostreams, display a fibroblastic-like morphology and express proteins typical of mesenchymal cells. The knockout of Col1a1 from tumoral cells eliminated oncostreams from tumors and delayed tumor progression. These data suggest that tumor cells expressing mesenchymal genes regulate the organization of mesenchymal multicellular structures, and determine glioma progression. We propose that inhibiting mesenchymal transformation of glioma cells will assist in the treatment of glioblastoma.

scholarly journals EphA2 super-enhancer promotes tumor progression by recruiting FOSL2 and TCF7L2 to activate the target gene EphA2

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Shuang Cui ◽  
Qiong Wu ◽  
Ming Liu ◽  
Mu Su ◽  
ShiYou Liu ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Tumor Cells ◽  
Target Gene ◽  
Super Enhancer ◽  
Proliferation And Metastasis ◽  
Active Transcription ◽  
Hct 116 ◽  
Large Clusters

AbstractSuper-enhancers or stretch enhancers (SEs) consist of large clusters of active transcription enhancers which promote the expression of critical genes that define cell identity during development and disease. However, the role of many super-enhancers in tumor cells remains unclear. This study aims to explore the function and mechanism of a new super-enhancer in various tumor cells. A new super-enhancer that exists in a variety of tumors named EphA2-Super-enhancer (EphA2-SE) was found using multiple databases and further identified. CRISPR/Cas9-mediated deletion of EphA2-SE results in the significant downregulation of its target gene EphA2. Mechanistically, we revealed that the core active region of EphA2-SE comprises E1 component enhancer, which recruits TCF7L2 and FOSL2 transcription factors to drive the expression of EphA2, induce cell proliferation and metastasis. Bioinformatics analysis of RNA-seq data and functional experiments in vitro illustrated that EphA2-SE deletion inhibited cell growth and metastasis by blocking PI3K/AKT and Wnt/β-catenin pathway in HeLa, HCT-116 and MCF-7 cells. Overexpression of EphA2 in EphA2-SE−/− clones rescued the effect of EphA2-SE deletion on proliferation and metastasis. Subsequent xenograft animal model revealed that EphA2-SE deletion suppressed tumor proliferation and survival in vivo. Taken together, these findings demonstrate that EphA2-SE plays an oncogenic role and promotes tumor progression in various tumors by recruiting FOSL2 and TCF7L2 to drive the expression of oncogene EphA2.

scholarly journals A Semi-Empirical Model for Predicting Frost Properties

Processes ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 412
Author(s):  
Shao-Ming Li ◽  
Kai-Shing Yang ◽  
Chi-Chuan Wang
Keyword(s):  
Thermal Conductivity ◽  
Linear Programming ◽  
Numerical Model ◽  
Empirical Model ◽  
Quantitative Method ◽  
Predictive Ability ◽  
Dimensionless Temperature ◽  
Crystal Shape ◽  
Proposed Model ◽  
Semi Empirical

In this study, a quantitative method for classifying the frost geometry is first proposed to substantiate a numerical model in predicting frost properties like density, thickness, and thermal conductivity. This method can recognize the crystal shape via linear programming of the existing map for frost morphology. By using this method, the frost conditions can be taken into account in a model to obtain the corresponding frost properties like thermal conductivity, frost thickness, and density for specific frost crystal. It is found that the developed model can predict the frost properties more accurately than the existing correlations. Specifically, the proposed model can identify the corresponding frost shape by a dimensionless temperature and the surface temperature. Moreover, by adopting the frost identification into the numerical model, the frost thickness can also be predicted satisfactorily. The proposed calculation method not only shows better predictive ability with thermal conductivities, but also gives good predictions for density and is especially accurate when the frost density is lower than 125 kg/m3. Yet, the predictive ability for frost density is improved by 24% when compared to the most accurate correlation available.

scholarly journals Iron-Bound Lipocalin-2 from Tumor-Associated Macrophages Drives Breast Cancer Progression Independent of Ferroportin

Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 180
Author(s):  
Christina Mertens ◽  
Matthias Schnetz ◽  
Claudia Rehwald ◽  
Stephan Grein ◽  
Eiman Elwakeel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Lung Metastases ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Lipocalin 2 ◽  
Tumor Associated Macrophages

Macrophages supply iron to the breast tumor microenvironment by enforced secretion of lipocalin-2 (Lcn-2)-bound iron as well as the increased expression of the iron exporter ferroportin (FPN). We aimed at identifying the contribution of each pathway in supplying iron for the growing tumor, thereby fostering tumor progression. Analyzing the expression profiles of Lcn-2 and FPN using the spontaneous polyoma-middle-T oncogene (PyMT) breast cancer model as well as mining publicly available TCGA (The Cancer Genome Atlas) and GEO Series(GSE) datasets from the Gene Expression Omnibus database (GEO), we found no association between tumor parameters and Lcn-2 or FPN. However, stromal/macrophage-expression of Lcn-2 correlated with tumor onset, lung metastases, and recurrence, whereas FPN did not. While the total iron amount in wildtype and Lcn-2−/− PyMT tumors showed no difference, we observed that tumor-associated macrophages from Lcn-2−/− compared to wildtype tumors stored more iron. In contrast, Lcn-2−/− tumor cells accumulated less iron than their wildtype counterparts, translating into a low migratory and proliferative capacity of Lcn-2−/− tumor cells in a 3D tumor spheroid model in vitro. Our data suggest a pivotal role of Lcn-2 in tumor iron-management, affecting tumor growth. This study underscores the role of iron for tumor progression and the need for a better understanding of iron-targeted therapy approaches.

Sign in / Sign up

Export Citation Format

Share Document