scholarly journals The Development and Validation of a Novel 71-Gene Signature for Risk Stratification and Prognosis in Lower Grade Glioma

2021 ◽  
Author(s):  
Jianxiong He ◽  
Pinggen Li ◽  
Xianggan Wang ◽  
Feijun Chen ◽  
Weijun Wu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hierarchical Clustering ◽  
Clustering Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Lower Grade ◽  
Good Prediction ◽  
Hierarchical Clustering Analysis ◽  
Gene Score ◽  
Genome Atlas

Abstract Background: Lower-grade gliomas (LGG) are a diverse group of primary brain tumors with relatively poor overall survival in young adults. In this study, we aimed to establish novel method that are effectively predictive of prognosis of LGG patients. Methods: We detected and validated prognosis-associated genes using gene expression and c`Clinical data of LGG patients from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. We then established a novel prognostic 71-gene score and 17-gene nomograms and analyzed their relationship with overall survival (OS) and relapse-free survival (RFS) in LGG patients. We also performed Gene Set Enrichment Analysis to investigate the altered signalling pathways associated with the 71-gene score phenotype and hierarchical clustering analysis of 71 genes to detect subgroups of LGG patients with distinct clinical characteristics. Results: We identified 1489 genes significantly correlated with patients’ prognosis in LGG. The 71-gene score was predictive of favourable OS and RFS in LGG patients independently of clinicopathological characteristics. The wnt signalling pathway, glutathione metabolism, primary immunodeficiency, galactose metabolism were the potential pathways involved in the prognostication of the 71-gene score. Hierarchical clustering analysis of the 71 genes revealed three subgroups of LGG patients in the TCGA dataset. The cluster2 LGG tumours were associated with higher grade, more frequent radiation therapy, poorer OS and RFS than cluster1 and cluster3 tumours. The 71-gene nomogram incorporating the survival‐related clinical factors showed good prediction accuracies for overall survival, 3-year and 5‐year survival (area under curve [AUC] = 0.79, 0.67 and 0.75 respectively). Conclusions: The 71-gene nomogram may turn out to be a useful and robust method to remarkably ameliorate the prognostic prediction in LGG.

A Novel 23-Gene Expression Signature is Predictor of Inferior Prognosis in Melanoma

2021 ◽  
Author(s):  
Min Du ◽  
Ling Ma ◽  
Fan Zhang ◽  
Dong Li
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Hierarchical Clustering ◽  
Expression Profiles ◽  
Gene Expression Signature ◽  
The Cancer Genome Atlas ◽  
Risk Scores ◽  
Gene Score ◽  
Survival Probabilities ◽  
Melanoma Patients

Abstract Background: Melanoma is a serious form of skin cancer that begins in melanocytes. Metastasis, somatic mutations and gene expression profiles are important prognostic factors for melanoma patients. However, accurate prediction of patient prognosis remains an unsolved problem for the disease. This study was to develop a novel gene profile to accurately classify melanoma patients into subgroups with different survival probabilities. Methods: Survival-related genes were determined by Kaplan–Meier survival analysis and multivariate analysis using the expression and clinical data of 467 melanoma patients from The Cancer Genome Atlas (TCGA) database and validated in an independent Gene Expression Omnibus (GEO) dataset. Feature selection was performed by the Least Absolute Shrinkage and Selection Operator (LASSO) method. A prognostic 23-gene score was established and compared with two known gene-expression risk scores. The stratification of melanoma patients was performed by unsupervised hierarchical clustering of 23 gene expression levels to identify clusters of melanoma patients with different survival probabilities. Results: The LASSO model comprising 23 genes was considered as the optimal model. The 23-gene score was associated with increased mortality in melanoma patients regardless of clinicopathological characteristics. Hierarchical clustering analysis of the 23 genes revealed three subgroups of melanoma patients. The cluster3 melanoma tumours were associated with higher 23-gene score and poorer overall survival than cluster1 and cluster2 tumours. The 23-gene score had higher area under curve (0.76) than the 8-gene risk score and IRGs score (0.58 and 0.59) in the prediction of overall survival of melanoma patients. Conclusions: The 23-gene score is superior to the two established prognostic gene signatures in the prediction of prognosis of melanoma patients.

scholarly journals RUNX1 and REXO2 are associated with the heterogeneity and prognosis of IDH wild type lower grade glioma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haiwei Wang ◽  
Xinrui Wang ◽  
Liangpu Xu ◽  
Ji Zhang ◽  
Hua Cao
Keyword(s):  
Transcription Factor ◽  
Low Frequency ◽  
Tumor Grade ◽  
The Cancer Genome Atlas ◽  
Lower Grade ◽  
Wild Type ◽  
Lower Grade Glioma ◽  
Cancer Genome Atlas ◽  
Worse Prognosis ◽  
Genome Atlas

AbstractBased on isocitrate dehydrogenase (IDH) alterations, lower grade glioma (LGG) is divided into IDH mutant and wild type subgroups. However, the further classification of IDH wild type LGG was unclear. Here, IDH wild type LGG patients in The Cancer Genome Atlas and Chinese Glioma Genome Atlas were divided into two sub-clusters using non-negative matrix factorization. IDH wild type LGG patients in sub-cluster2 had prolonged overall survival and low frequency of CDKN2A alterations and low immune infiltrations. Differentially expressed genes in sub-cluster1 were positively correlated with RUNX1 transcription factor. Moreover, IDH wild type LGG patients with higher stromal score or immune score were positively correlated with RUNX1 transcription factor. RUNX1 and its target gene REXO2 were up-regulated in sub-cluster1 and associated with the worse prognosis of IDH wild type LGG. RUNX1 and REXO2 were associated with the higher immune infiltrations. Furthermore, RUNX1 and REXO2 were correlated with the worse prognosis of LGG or glioma. IDH wild type LGG in sub-cluster2 was hyper-methylated. REXO2 hyper-methylation was associated with the favorable prognosis of LGG or glioma. At last, we showed that, age, tumor grade and REXO2 expression were independent prognostic factors in IDH wild type LGG.

scholarly journals The visual categorization of production automotive seats on descriptors of comfort

Work ◽  
2021 ◽  
Vol 68 (s1) ◽  
pp. S69-S85
Author(s):  
Tugra Erol ◽  
Cyriel Diels ◽  
James Shippen ◽  
Dale Richards
Keyword(s):  
Hierarchical Clustering ◽  
Clustering Analysis ◽  
The Other ◽  
Visual Design ◽  
Hierarchical Clustering Analysis ◽  
Card Sorting ◽  
Design Attributes ◽  
Comfort Perception ◽  
Automotive Production

BACKGROUND: The role of appearance of automotive seats on perceived comfort and comfort expectancy has been acknowledged in previous research but it has not been investigated in depth. OBJECTIVE: To identify the effects of the appearance of production automotive seats, based on the hypothesis that visual design differentiations are affective in creating comfort expectations. The significance of the descriptors Sporty, Luxurious and Comfortable and the associated visual design attributes was of interest. METHOD: Images from 38 automotive production seats were used in an image-based card sorting app (qCard) with a total of 24 participants. Participants were asked to categorize the different seat designs varying from 1: least, to 9: most for all three descriptors.The resulting data was analyzed using hierarchical clustering analysis. RESULTS: The results indicated that the perceived Sporty, Luxurious and Comfortable were descriptor items that significantly differentiated seats with certain design attributes. It was found that for the Sporty perception the integrated headrest design and angular shapes were key. On the other hand, the Comfort perception was characterised by seating with a separate headrest and rounded seat back/cushion shapes. CONCLUSIONS: For seat design processes, the method enables a practical way to identify elements conveying Sporty, Comfortable and Luxurious perception.

scholarly journals Exploration and validation of a novel prognostic signature based on comprehensive bioinformatics analysis in hepatocellular carcinoma

2020 ◽  
Vol 40 (11) ◽  
Author(s):  
Xiaofei Wang ◽  
Jie Qiao ◽  
Rongqi Wang
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Risk Score ◽  
Expression Profiles ◽  
Univariate Analysis ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Good Prediction ◽  
Expression Levels

Abstract The present study aimed to construct a novel signature for indicating the prognostic outcomes of hepatocellular carcinoma (HCC). Gene expression profiles were downloaded from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. The prognosis-related genes with differential expression were identified with weighted gene co-expression network analysis (WGCNA), univariate analysis, the least absolute shrinkage and selection operator (LASSO). With the stepwise regression analysis, a risk score was constructed based on the expression levels of five genes: Risk score = (−0.7736* CCNB2) + (1.0083* DYNC1LI1) + (−0.6755* KIF11) + (0.9588* SPC25) + (1.5237* KIF18A), which can be applied as a signature for predicting the prognosis of HCC patients. The prediction capacity of the risk score for overall survival was validated with both TCGA and ICGC cohorts. The 1-, 3- and 5-year ROC curves were plotted, in which the AUC was 0.842, 0.726 and 0.699 in TCGA cohort and 0.734, 0.691 and 0.700 in ICGC cohort, respectively. Moreover, the expression levels of the five genes were determined in clinical tumor and normal specimens with immunohistochemistry. The novel signature has exhibited good prediction efficacy for the overall survival of HCC patients.

scholarly journals A comprehensive analysis of the angiogenesis-related genes in glioblastoma multiforme vs. brain lower grade glioma

2020 ◽  
Vol 78 (1) ◽  
pp. 34-38
Author(s):  
Burcu BITERGE-SUT
Keyword(s):  
Glioblastoma Multiforme ◽  
Malignant Gliomas ◽  
Genetic Alterations ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Lower Grade ◽  
Nonsense Mutations ◽  
Lower Grade Glioma ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Abstract Brain tumors are one of the most common causes of cancer-related deaths around the world. Angiogenesis is critical in high-grade malignant gliomas, such as glioblastoma multiforme. Objective: The aim of this study is to comparatively analyze the angiogenesis-related genes, namely VEGFA, VEGFB, KDR, CXCL8, CXCR1 and CXCR2 in LGG vs. GBM to identify molecular distinctions using datasets available on The Cancer Genome Atlas (TCGA). Methods: DNA sequencing and mRNA expression data for 514 brain lower grade glioma (LGG) and 592 glioblastoma multiforme (GBM) patients were acquired from The Cancer Genome Atlas (TCGA), and the genetic alterations and expression levels of the selected genes were analyzed. Results: We identified six distinct KDR mutations in the LGG patients and 18 distinct KDR mutations in the GBM patients, including missense and nonsense mutations, frame shift deletion and altered splice region. Furthermore, VEGFA and CXCL8 were significantly overexpressed within GBM patients. Conclusions: VEGFA and CXCL8 are important factors for angiogenesis, which are suggested to have significant roles during tumorigenesis. Our results provide further evidence that VEGFA and CXCL8 could induce angiogenesis and promote LGG to progress into GBM. These findings could be useful in developing novel targeted therapeutics approaches in the future.

Sign in / Sign up

Export Citation Format

Share Document