scholarly journals Establishment of an Immune-Related Gene Signature for Risk Stratification for Patients with Glioma

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Jimin He ◽  
Chun Zeng ◽  
Yong Long
Keyword(s):  
Risk Stratification ◽  
Prognostic Model ◽  
Cox Regression ◽  
Prognostic Indicator ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Survival Prediction ◽  
Cox Regression Analysis ◽  
Immune Related Genes ◽  
Genome Atlas

Glioma is a frequently seen primary malignant intracranial tumor, characterized by poor prognosis. The study is aimed at constructing a prognostic model for risk stratification in patients suffering from glioma. Weighted gene coexpression network analysis (WGCNA), integrated transcriptome analysis, and combining immune-related genes (IRGs) were used to identify core differentially expressed IRGs (DE IRGs). Subsequently, univariate and multivariate Cox regression analyses were utilized to establish an immune-related risk score (IRRS) model for risk stratification for glioma patients. Furthermore, a nomogram was developed for predicting glioma patients’ overall survival (OS). The turquoise module ( cor = 0.67 ; P < 0.001 ) and its genes ( n = 1092 ) were significantly pertinent to glioma progression. Ultimately, multivariate Cox regression analysis constructed an IRRS model based on VEGFA, SOCS3, SPP1, and TGFB2 core DE IRGs, with a C-index of 0.811 (95% CI: 0.786-0.836). Then, Kaplan-Meier (KM) survival curves revealed that patients presenting high risk had a dismal outcome ( P < 0.0001 ). Also, this IRRS model was found to be an independent prognostic indicator of gliomas’ survival prediction, with HR of 1.89 (95% CI: 1.252-2.85) and 2.17 (95% CI: 1.493-3.14) in the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) datasets, respectively. We established the IRRS prognostic model, capable of effectively stratifying glioma population, convenient for decision-making in clinical practice.

CTNI-39. IDENTIFICATION OF AN AUTOPHAGY-RELATED GENE SIGNATURE AND ESTABLISHMENT OF A NOMOGRAM PREDICTING SURVIVAL OF LOWER-GRADE GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi68-vi68
Author(s):  
Lei Wen ◽  
hui Wang ◽  
Mingyao Lai ◽  
Changguo Shan ◽  
Linbo Cai
Keyword(s):  
Risk Stratification ◽  
Cox Regression ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Medical Decision ◽  
Survival Prediction ◽  
Lower Grade ◽  
Related Gene ◽  
Prognostic Signature ◽  
Genome Atlas

Abstract OBJECTIVE The aim of our study was to establish an autophagy-related signature for individualized risk stratification and prognosis prediction in LGG. METHODS RNA-sequencing data from The Cancer Genome Atlas (TCGA), Genome Tissue Expression (GTEx), and Chinese Glioma Genome Atlas (CGGA) were used. The 232 ARGs were obtained from the Human Autophagy Database (HADb). Univariate and Lasso regression were employed to identify differentially expressed autophagy-related genes (ARGs) and establish a prognostic signature whose performance was evaluated by Kaplan-Meier curve, receiver operating characteristic (ROC), Harrell’s concordance index (C-index) and calibration curve. RESULTS Fifty-three autophagy-related DEGs were identified. Four autophagy-related genes (DIRAS3, GNAI3, PTK6, and BIRC5) were selected to establish the prognostic signature and verified in the CGGA validation cohorts. Univariate and multivariate Cox regression indicated that the autophagy signature (HR, 95%CI, P) was an independent predictor of prognosis in LGG. Finally, a prognostic nomogram incorporating age, grade, targeted therapy, new event, tumor status and autophagy signature achieved excellent predicative performance (AUC 0.907, 0.865 and 0.858 for 1-year, 3-year and 5-year survival, respectively) verified by Time-dependent ROC, C-index (0.844, 95% CI, 0.799 to 0.889; P = 1.01e-12) and calibration plots. CONCLUSION The present study constructed a robust four autophagy-related gene signature. A prognostic nomogram in risk stratification and prediction of overall survival in LGG was established. The findings may be beneficial to individualized survival prediction and medical decision-making for LGG.

scholarly journals Weighted Gene Coexpression Network Analysis Reveals Cancer Stem Cell-Associated Metabolic Gene Signature in Glioma

2021 ◽  
Author(s):  
Yan Tang ◽  
Yao Jiang ◽  
Dan Zhang ◽  
Jia Fan ◽  
Juan Yao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Network Analysis ◽  
Risk Stratification ◽  
Cancer Stem Cell ◽  
Prognostic Model ◽  
Cox Regression ◽  
Roc Curves ◽  
Gene Signature ◽  
Metabolic Gene ◽  
Genome Atlas

Abstract Background: Isocitrate dehydrogenase (IDH) mutant glioma patients have a favorable prognosis, accompanying with metabolic alterations and glioma cell dedifferentiation. Recently, mRNA expression-based stemness index (mRNAsi) characteristic relation to IDH status of gliomas has yet illuminated. Thus, we aimed to establish a cancer stem cell-associated metabolic gene signature for risk stratification of gliomas. Methods: The glioma samples came from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases. Next, we performed the differential expression analysis between IDH mutant and IDH wild-type gliomas and also conducted weighted gene correlation network analysis (WGCNA) for determining the modules associated with cancer stem cell trait. Subsequently, multivariate Cox regression analysis with the Akaike information criterion (AIC) algorithm was employed to establish a stemness-related metabolic gene signature, which was validated using time-dependent receiver operating characteristic (ROC) curves and concordance index (C-index). Also, we developed a nomogram based on clinical traits and prognostic model. Additionally, according to the results of immunohistochemistry (IHC) staining, the protein levels of gene signature were consistent with the genes expression’s direction.Results: Low expression of mRNAsi was capable of predicting the unfavourable OS of gliomas with a 5-year survival rate of 14.08%. The blue module and its 1466 genes were pertinent to mRNAsi characteristic. Next, Kaplan-Meier (KM) survival curves revealed that cancer stem cell-associated metabolic genes exerted impact on gliomas’ prognosis. Subsequently, univariate and multivariate Cox regression analyses were implemented, and gene signature (LCAT, UST, GALNT13, and SMPD3) was constructed, with C-index of 0.798 (95%CI: 0.769-0.827). Notably, the prognostic model presented a superior predictive value for gliomas’ survival, with the area under the curve (AUC) of ROC curves at 1-year, 3-year as well as 5-year time-point of 0.845, 0.85 and 0.811, respectively. And forest plot uncovered its role as a potential independent predictor for gliomas (HR=2.840, 95%CI: 1.961-4.113, P <0.001). Nomogram also presented superior predictive performance for gliomas’ OS. Conclusion: The gene signature (LCAT, UST, GALNT13, and SMPD3) can be used for risk stratification and also can serve as an independent prognostic factor of glioma patients.

scholarly journals A Novel 10-Gene Signature Predicts Poor Prognosis in Low Grade Glioma

2021 ◽  
Vol 20 ◽  
pp. 153303382199208
Author(s):  
Wentao Liu ◽  
Jiaxuan Zou ◽  
Rijun Ren ◽  
Jingping Liu ◽  
Gentang Zhang ◽  
...  
Keyword(s):  
Risk Score ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Gene Signature ◽  
Low Grade Glioma ◽  
The Cancer Genome Atlas ◽  
Low Grade ◽  
Normal Brain ◽  
Cox Regression Analysis ◽  
Genome Atlas

Aim: Low grade glioma (LGG) is a lethal brain cancer with relatively poor prognosis in young adults. Thus, this study was performed to develop novel molecular biomarkers to effectively predict the prognosis of LGG patients and finally guide treatment decisions. Methods: survival-related genes were determined by Kaplan-Meier survival analysis and multivariate Cox regression analysis using the expression and clinical data of 506 LGG patients from The Cancer Genome Atlas (TCGA) database and independently validated in a Chinese Glioma Genome Atlas (CGGA) dataset. A prognostic risk score was established based on a linear combination of 10 gene expression levels using the regression coefficients of the multivariate Cox regression models. GSEA was performed to analyze the altered signaling pathways between the high and low risk groups stratified by median risk score. Results: We identified a total of 1489 genes significantly correlated with patients’ prognosis in LGG. The top 5 protective genes were DISP2, CKMT1B, AQP7, GPR162 and CHGB, the top 5 risk genes were SP1, EYA3, ZSCAN20, ITPRIPL1 and ZNF217 in LGG. The risk score was predictive of poor overall survival and relapse-free survival in LGG patients. Pathways of small cell lung cancer, pathways in cancer, chronic myeloid leukemia, colorectal cancer were the top 4 most enriched pathways in the high risk group. SP1, EYA3, ZSCAN20, ITPRIPL1, ZNF217 and GPR162 were significantly up-regulated, while DISP2, CKMT1B, AQP7 were down-regulated in 523 LGG tissues as compared to 1141 normal brain controls. Conclusions: The 10-gene signature may become novel prognostic and diagnostic biomarkers to considerably improve the prognostic prediction in LGG.

scholarly journals Development of a prognostic signature for esophageal cancer based on nine immune related genes

2020 ◽  
Author(s):  
zhi Zhang ◽  
cheng chen ◽  
ying fang ◽  
sheng Li ◽  
xiaohua Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Esophageal Cancer ◽  
Prognostic Model ◽  
Cox Regression ◽  
Risk Group ◽  
The Cancer Genome Atlas ◽  
Receptor Interaction ◽  
Prognostic Signature ◽  
Cox Regression Analysis ◽  
Immune Related Genes

Abstract Background: Function of the immune system is correlated with the prognosis of the tumor. The effect of immune microenvironment on esophageal cancer (EC) development has not been fully investigated. Methods: This study aimed to explore a prognostic model based on immune-related genes (IRGs) for EC. We obtained the RNA-seq dataset and clinical information of EC from the Cancer Genome Atlas (TCGA). Results: We identified 247 upregulated IRGs and 56 downregulated IRGs. Pathway analysis revealed that the most differentially expressed IRGs were enriched in Cytokine-cytokine receptor interaction. We further screened 13 survival-related IRGs and constructed regulatory networks involving related transcription factors (TFs). Finally, a prognostic model was constructed with 9 IRGs (HSPA6, S100A12, CACYBP, NOS2, DKK1, OSM ,STC2 ,NGPTL3 and NR2F2) by multivariate Cox regression analysis. The patients were classified into two subgroups with different outcomes. When adjusted with clinical factors, this model was verified as an independent predictor, which performed accurately in prognostic prediction. Next, M0 and M2 macrophages and activated mast cells were significantly enriched in high-risk group, while CD8 T cells and regulatory T cells (Tregs) were significantly enriched in low-risk group. Conclusions: Prognosis related IRGs were identified and a prognostic signature for esophageal cancer based on nine IRGs was developed.

scholarly journals Development of a prognostic model for esophageal cancer based on nine immune related genes

2020 ◽  
Author(s):  
Zhi Zhang ◽  
Cheng Chen ◽  
Ying Fang ◽  
Sheng Li ◽  
Xiaohua Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Esophageal Cancer ◽  
Regulatory Networks ◽  
Prognostic Model ◽  
Cox Regression ◽  
Risk Group ◽  
The Cancer Genome Atlas ◽  
Receptor Interaction ◽  
Cox Regression Analysis ◽  
Immune Related Genes

Abstract Background: Function of the immune system is correlated with the prognosis of the tumor. The effect of immune microenvironment on esophageal cancer (EC) development has not been fully investigated. Methods: This study aimed to explore a prognostic model based on immune-related genes (IRGs) for EC. We obtained the RNA-seq dataset and clinical information of EC from the Cancer Genome Atlas (TCGA). Results: We identified 247 upregulated IRGs and 56 downregulated IRGs. Pathway analysis revealed that the most differentially expressed IRGs were enriched in Cytokine-cytokine receptor interaction. We further screened 13 survival-related IRGs and constructed regulatory networks involving related transcription factors (TFs). Finally, a prognostic model was constructed with 9 IRGs (HSPA6, S100A12, CACYBP, NOS2, DKK1, OSM ,STC2 ,NGPTL3 and NR2F2) by multivariate Cox regression analysis. The patients were classified into two subgroups with different outcomes. When adjusted with clinical factors, this model was verified as an independent predictor, which performed accurately in prognostic prediction. Next, M0 and M2 macrophages and activated mast cells were significantly enriched in high-risk group, while CD8 T cells and regulatory T cells (Tregs) were significantly enriched in low-risk group. Conclusions: These molecules may serve as potential therapeutic targets and biomarkers for the new-immunotherapy of EC.

scholarly journals A Potential Prognostic Gene Signature for Predicting Survival for Glioblastoma Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Ziming Hou ◽  
Jun Yang ◽  
Hao Wang ◽  
Dongyuan Liu ◽  
Hongbing Zhang
Keyword(s):  
Prognostic Model ◽  
Cox Regression ◽  
Risk Groups ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Prognostic Models ◽  
Training Set ◽  
Prognostic Gene ◽  
Prognostic Gene Signature ◽  
Genome Atlas

Objective. This study aimed to screen prognostic gene signature of glioblastoma (GBM) to construct prognostic model.Methods. Based on the GBM information in the Cancer Genome Atlas (TCGA, training set), prognostic genes (Set X) were screened by Cox regression. Then, the optimized prognostic gene signature (Set Y) was further screened by the Cox-Proportional Hazards (Cox-PH). Next, two prognostic models were constructed: model A was based on the Set Y; model B was based on part of the Set X. The samples were divided into low- and high-risk groups according to the median prognosis index (PI). GBM datasets in Gene Expression Ominous (GEO, GSE13041) and Chinese Glioma Genome Atlas (CGGA) were used as the testing datasets to confirm the prognostic models constructed based on TCGA.Results. We identified that the prognostic 14-gene signature was significantly associated with the overall survival (OS) in the TCGA. In model A, patients in high- and low-risk groups showed the significantly different OS (P = 7.47 × 10−9, area under curve (AUC) 0.995) and the prognostic ability were also confirmed in testing sets (P=0.0098 and 0.037). The model B in training set was significant but failed in testing sets.Conclusion. The prognostic model which was constructed based on the prognostic 14-gene signature presented a high predictive ability for GBM. The 14-gene signature may have clinical implications in the subclassification of GBM.

scholarly journals Development of a prognostic signature for esophageal cancer based on nine immune related genes

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhi Zhang ◽  
Cheng Chen ◽  
Ying Fang ◽  
Sheng Li ◽  
Xiaohua Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Esophageal Cancer ◽  
Prognostic Model ◽  
Cox Regression ◽  
Risk Group ◽  
The Cancer Genome Atlas ◽  
Receptor Interaction ◽  
Prognostic Signature ◽  
Cox Regression Analysis ◽  
Immune Related Genes

Abstract Background Function of the immune system is correlated with the prognosis of the tumor. The effect of immune microenvironment on esophageal cancer (EC) development has not been fully investigated. Methods This study aimed to explore a prognostic model based on immune-related genes (IRGs) for EC. We obtained the RNA-seq dataset and clinical information of EC from the Cancer Genome Atlas (TCGA). Results We identified 247 upregulated IRGs and 56 downregulated IRGs. Pathway analysis revealed that the most differentially expressed IRGs were enriched in Cytokine-cytokine receptor interaction. We further screened 13 survival-related IRGs and constructed regulatory networks involving related transcription factors (TFs). Finally, a prognostic model was constructed with 9 IRGs (HSPA6, S100A12, CACYBP, NOS2, DKK1, OSM, STC2, NGPTL3 and NR2F2) by multivariate Cox regression analysis. The patients were classified into two subgroups with different outcomes. When adjusted with clinical factors, this model was verified as an independent predictor, which performed accurately in prognostic prediction. Next, M0 and M2 macrophages and activated mast cells were significantly enriched in high-risk group, while CD8 T cells and regulatory T cells (Tregs) were significantly enriched in low-risk group. Conclusions Prognosis related IRGs were identified and a prognostic signature for esophageal cancer based on nine IRGs was developed.

scholarly journals Development of a prognostic model for esophageal cancer based on nine immune related genes

2020 ◽  
Author(s):  
zhi Zhang ◽  
cheng chen ◽  
ying fang ◽  
sheng Li ◽  
xiaohua Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Esophageal Cancer ◽  
Regulatory Networks ◽  
Prognostic Model ◽  
Cox Regression ◽  
Risk Group ◽  
The Cancer Genome Atlas ◽  
Receptor Interaction ◽  
Cox Regression Analysis ◽  
Immune Related Genes

Abstract Background: Function of the immune system is correlated with the prognosis of the tumor. The effect of immune microenvironment on esophageal cancer (EC) development has not been fully investigated. This study aimed to explore a prognostic model based on immune-related genes (IRGs) for EC. Methods: We obtained the RNA-seq dataset and clinical information of EC from the Cancer Genome Atlas (TCGA). We identified 247 upregulated IRGs and 56 downregulated IRGs. Pathway analysis revealed that the most differentially expressed IRGs were enriched in Cytokine-cytokine receptor interaction. We further screened 13 survival-related IRGs and constructed regulatory networks involving related transcription factors (TFs). Finally, a prognostic model was constructed with 9 IRGs (HSPA6, S100A12, CACYBP, NOS2, DKK1, OSM ,STC2 ,NGPTL3 and NR2F2) by multivariate Cox regression analysis. Results: The patients were classified into two subgroups with different outcomes. When adjusted with clinical factors, this model was verified as an independent predictor, which performed accurately in prognostic prediction. Next, M0 and M2 macrophages and activated mast cells were significantly enriched in high-risk group, while CD8 T cells and regulatory T cells (Tregs) were significantly enriched in low-risk group. Conclusion: These molecules may serve as potential therapeutic targets and biomarkers for the new-immunotherapy of EC.

scholarly journals Identification of prognostic alternative splicing events in sarcoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hongshuai Li ◽  
Jie Yang ◽  
Guohui Yang ◽  
Jia Ren ◽  
Yu Meng ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Area Under The Curve ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis ◽  
Functional Roles ◽  
Cancer Pathogenesis ◽  
Rare Malignancy

AbstractSarcoma is a rare malignancy with unfavorable prognoses. Accumulating evidence indicates that aberrant alternative splicing (AS) events are generally involved in cancer pathogenesis. The aim of this study was to identify the prognostic value of AS-related survival genes as potential biomarkers, and highlight the functional roles of AS events in sarcoma. RNA-sequencing and AS-event datasets were downloaded from The Cancer Genome Atlas (TCGA) sarcoma cohort and TCGA SpliceSeq, respectively. Survival-related AS events were further assessed using a univariate analysis. A multivariate Cox regression analysis was also performed to establish a survival-gene signature to predict patient survival, and the area-under-the-curve method was used to evaluate prognostic reliability. KOBAS 3.0 and Cytoscape were used to functionally annotate AS-related genes and to assess their network interactions. We detected 9674 AS events in 40,184 genes from 236 sarcoma samples, and the 15 most significant genes were then used to construct a survival regression model. We further validated the involvement of ten potential survival-related genes (TUBB3, TRIM69, ZNFX1, VAV1, KCNN2, VGLL3, AK7, ARMC4, LRRC1, and CRIP1) in the occurrence and development of sarcoma. Multivariate survival model analyses were also performed, and validated that a model using these ten genes provided good classifications for predicting patient outcomes. The present study has increased our understanding of AS events in sarcoma, and the gene-based model using AS-related events may serve as a potential predictor to determine the survival of sarcoma patients.

scholarly journals Identification of a Glycolysis-Related Gene Signature for Survival Prediction of Ovarian Cancer Patients

2020 ◽  
Author(s):  
Dai Zhang ◽  
Si Yang ◽  
Yiche Li ◽  
Meng Wang ◽  
Jia Yao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Risk Model ◽  
Cox Regression ◽  
Expression Profiles ◽  
Gynecological Cancer ◽  
Predictive Ability ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Survival Prediction ◽  
Test Sets

Abstract Background: Ovarian cancer (OV) is deemed as the most lethal gynecological cancer in women. The aim of this study was construct an effective gene prognostic model for OV patients.Methods: The expression profiles of glycolysis-related genes (GRGs) and clinical data of patients with OV were extracted from The Cancer Genome Atlas (TCGA) database. Univariate, multivariate, and least absolute shrinkage and selection operator Cox regression analyses were conducted, and a prognostic signature based on GRGs was constructed. The predictive ability of the signature was analyzed in training and test sets.Results: Based on nine GRGs (ISG20, CITED2, PYGB, IRS2, ANGPTL4, TGFBI, LHX9, PC, and DDIT4), a gene risk signature was identified to predict the outcome of patients with OV. The signature showed a good prognostic ability for OV, particularly high-grade OV, in the TCGA dataset, with areas under the curve of 0.709, 0.762, and 0.808 for 3-, 5- and 10-year survival, respectively. Similar results were found in the test sets, and the signature was also an independent prognostic factor. Moreover, a nomogram combining the prediction model and clinical factors was constructed.Conclusion: Our study established a nine-GRG risk model and a nomogram to better perform on OV patients’ survival prediction. The risk model represents a promising and independent prognostic predictor for OV patients. Moreover, our study of GRGs could offer guidances for underlying mechanisms explorations in the future.

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