scholarly journals High Expression of C1ORF112 Predicts a Poor Outcome: A Potential Target for the Treatment of Low-Grade Gliomas

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhe Zhang ◽  
Zilong Tan ◽  
Qiaoli Lv ◽  
Lichong Wang ◽  
Kai Yu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Analysis ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Low Grade ◽  
Poor Overall Survival ◽  
Genetic Changes ◽  
Low Grade Gliomas ◽  
Genome Atlas

Background: Glioma is the most common primary tumor of the central nervous system and is associated with poor overall survival, creating an urgent need to identify survival-associated biomarkers. C1ORF112, an alpha-helical protein, is overexpressed in some cancers; however, its prognostic role has not yet been explored in gliomas. Thus, in this study, we attempted to address this by determining the prognostic value and potential function of C1ORF112 in low-grade gliomas (LGGs).Methods: The expression of C1ORF112 in normal and tumor tissues was analyzed using data from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Oncomine, and Rembrandt databases. The genetic changes of C1ORF112 in LGG were analyzed using cBioPortal. Survival analysis was used to evaluate the relationship between C1ORF112 expression and survival in patients with LGG. Correlation between immune infiltration and C1ORF112 expression was determined using Timer software. Additionally, data from three online platforms were integrated to identify the co-expressed genes of C1ORF112. The potential biological functions of C1ORF112 were investigated by enrichment analysis.Results: C1ORF112 mRNA was highly expressed in LGGs (p < 0.01). Area under the ROC curve (AUC) showed that the expression of C1ORF112 in LGG was 0.673 (95% confidence interval [CI] = 0.618–0.728). Kaplan-Meier survival analysis showed that patients with high C1ORF112 expression had lower OS than patients with low C1ORF112 expression (p < 0.05). Multivariate analysis showed that high expression of C1ORF112 was an independent prognostic factor for the overall survival in patients from TCGA and CGGA databases. C1ORF112 expression was positively correlated with six immunoinfiltrating cells (all p < 0.001). The enrichment analysis suggested the enrichment of C1ORF112 and co-expressed genes in cell cycle and DNA replication.Conclusion: This study suggested that C1ORF112 may be a prognostic biomarker and a potential immunotherapeutic target for LGG.

scholarly journals Tumor Mutational Burden Predicts Survival In Patients With Low Grade Gliomas Expressing Mutated IDH1

2020 ◽  
Author(s):  
Mahmoud S Alghamri ◽  
Rohit Thalla ◽  
Ruthvik Avvari ◽  
Ali Dabaja ◽  
Ayman Taher ◽  
...  
Keyword(s):  
Median Survival ◽  
Enrichment Analysis ◽  
Gene Signature ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Low Grade ◽  
Low Grade Gliomas ◽  
Mutational Burden ◽  
Tumor Mutational Burden ◽  
Genome Atlas

ABSTRACTGliomas are the most common primary brain tumors. High Grade Gliomas have a median survival of 18 months, while Low Grade Gliomas (LGG) have a median survival of ∼7.3 years. Seventy-six percent of patients with LGG express mutated isocitrate dehydrogenase (mIDH1) enzyme (IDH1R132H). Survival of these patients ranges from 1-15 years, and tumor mutational burden ranges from 8 to 447 total somatic mutations per tumor. We tested the hypothesis that the tumor mutational burden would predict survival of patients with tumors bearing mIDH1R132H. We analyzed the effect of tumor mutational burden on patients’ survival using clinical and genomic data of 1199 glioma patients from The Cancer Genome Atlas and validated our results using the Chinese Glioma Genome Atlas. High tumor mutational burden negatively correlates with survival of patients with LGG harboring IDH1R132H (p<0.0001). This effect was significant for both Oligodendroglioma and Astrocytoma LGG-mIDH1 patients. In the TCGA data, median survival of the high mutational burden group was 76 months, while in the low mutational burden group it was 136 months; p<0.0001. There was no differential representation of frequently mutated genes (e.g., TP53, ATRX, CIC, FUBP) in either group. Gene set enrichment analysis revealed an enrichment in Gene Ontologies related to Cell cycle, DNA damage response in high vs low tumor mutational burden. Finally, we identified a 19 gene signature that predicts survival for patients from both databases. In summary, we demonstrate that tumor mutational burden is a powerful, robust, and clinically relevant prognostic factor of median survival in mIDH1 patients.

scholarly journals Six Immune Associated Genes Construct Prognostic Model Evaluate Low-Grade Glioma

2020 ◽  
Vol 11 ◽  
Author(s):  
Yin Qiu Tan ◽  
Yun Tao Li ◽  
Teng Feng Yan ◽  
Yang Xu ◽  
Bao Hui Liu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Risk Score ◽  
Survival Rates ◽  
Low Grade Glioma ◽  
The Cancer Genome Atlas ◽  
Low Grade ◽  
Sequencing Analysis ◽  
Six Genes ◽  
Genome Atlas ◽  
Overall Survival Rates

BackgroundThe immunotherapy of Glioma has always been a research hotspot. Although tumor associated microglia/macrophages (TAMs) proves to be important in glioma progression and drug resistance, our knowledge about how TAMs influence glioma remains unclear. The relationship between glioma and TAMs still needs further study.MethodsWe collected the data of TAMs in glioma from NCBI Gene Expression Omnibus (GEO) that included 20 glioma samples and 15 control samples from four datasets. Six genes were screened from the Differential Expression Gene through Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein–protein interaction (PPI) network and single-cell sequencing analysis. A risk score was then constructed based on the six genes and patients’ overall survival rates of 669 patients from The Cancer Genome Atlas (TCGA). The efficacy of the risk score in prognosis and prediction was verified in Chinese Glioma Genome Atlas (CGGA).ResultsSix genes, including CD163, FPR3, LPAR5, P2ry12, PLAUR, SIGLEC1, that participate in signal transduction and plasma membrane were selected. Half of them, like CD163, FPR3, SIGLEC1, were mainly expression in M2 macrophages. FPR3 and SIGLEC1 were high expression genes in glioma associated with grades and IDH status. The overall survival rates of the high risk score group was significantly lower than that of the low risk score group, especially in LGG.ConclusionJoint usage of the 6 candidate genes may be an effective method to diagnose and evaluate the prognosis of glioma, especially in Low-grade glioma (LGG).

scholarly journals The Cancer Genome Atlas expression profiles of low-grade gliomas

2014 ◽  
Vol 36 (4) ◽  
pp. E23 ◽  
Author(s):  
David D. Gonda ◽  
Vincent J. Cheung ◽  
Karra A. Muller ◽  
Amit Goyal ◽  
Bob S. Carter ◽  
...  
Keyword(s):  
Cpg Island ◽  
Expression Profiles ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Molecular Characteristics ◽  
Low Grade ◽  
Cpg Island Methylator Phenotype ◽  
Low Grade Gliomas ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Differentiating between low-grade gliomas (LGGs) of astrocytic and oligodendroglial origin remains a major challenge in neurooncology. Here the authors analyzed The Cancer Genome Atlas (TCGA) profiles of LGGs with the goal of identifying distinct molecular characteristics that would afford accurate and reliable discrimination of astrocytic and oligodendroglial tumors. They found that 1) oligodendrogliomas are more likely to exhibit the glioma-CpG island methylator phenotype (G-CIMP), relative to low-grade astrocytomas; 2) relative to oligodendrogliomas, low-grade astrocytomas exhibit a higher expression of genes related to mitosis, replication, and inflammation; and 3) low-grade astrocytic tumors harbor microRNA profiles similar to those previously described for glioblastoma tumors. Orthogonal intersection of these molecular characteristics with existing molecular markers, such as IDH1 mutation, TP53 mutation, and 1p19q status, should facilitate accurate and reliable pathological diagnosis of LGGs.

scholarly journals The Prognostic Value of Risk Score Based on Immunogenenomic Landscape Analysis in Glioma

2020 ◽  
Author(s):  
Haitao Luo ◽  
Kai Huang ◽  
Chuming Tao ◽  
Mioaojing Wu ◽  
Minhua Ye ◽  
...  
Keyword(s):  
Risk Score ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Low Grade ◽  
Clinical Prognosis ◽  
Cox Analysis ◽  
Genome Atlas

Abstract Background: Glioma is a lethal intracranial tumor, and inflammation plays an important role in the initiation and development of glioma. Hence, there is an urgent need to conduct a bioinformatics analysis of immune-related genes (IRGs) for glioma. The present study aims to explore the association of the risk score with clinical outcomes and predict the prognosis with glioma. Methods: In The Cancer Genome Atlas (TCGA) database, 462 low grade glioma (LGG) samples and 166 glioblastoma (GBM) samples were reviewed, and IRGs correlated with the prognosis were selected by performing a survival analysis and establishing a Cox regression model. The potential molecular mechanism of these IRGs were also explored with assistance of computational biology. The risk score based on seven survival-associated IRGs was determined with the help of the multivariable Cox analysis, the patients were divided into two subgroups according to their risk score. Results: It was found that these differentially expressed IRGs were involved with the cytokine-cytokine receptor through functional enrichment analysis. The risk score based on the seven IRGs (SSTR5、CXCL10、CCL13、SAA1、CCL21、CCL27 and HTR1A) performed well in predicting patient’s the overall survival (OS), and correlated with age, 1p/19q codeletion status, IDH status, and WHO grades, both in the training (TCGA) datasets and the validation ((Chinese Glioma Genome Atlas) CGGA) datasets. The risk score also could reflect infiltration through several types of immune cells. Conclusions: This present study screened some IRGs associated with the patient’s clinical characteristic and prognosis, connect to the immune repertoire, demonstrated the importance of the risk score as a promising biomarker for estimating the clinical prognosis of glioma.

scholarly journals Up-regulated Expression of MTHFD2 Correlates with Favorable Prognosis in LGG Patients: A Bioinformatic Analysis

2020 ◽  
Author(s):  
Lu-feng Shi ◽  
Qian Zhang ◽  
Xiao-ying Shou ◽  
Huan-jiang Niu
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Prognostic Factor ◽  
Potential Function ◽  
Enrichment Analysis ◽  
Histologic Grade ◽  
High Expression ◽  
Low Grade ◽  
Tumor Type ◽  
Cox Regression Analysis

Abstract Background Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) was found to be up-regulated in various cancers and has been identified as a potential target for cancer treatment, but the potential function of MTHFD2 in low-grade gliomas (LGG) has not been well-examined. This study initially revealed the potential function of MTHD2 and emphasized its importance in LGG. Methods We first explored the expression of MTHFD2 in LGG patients using Oncomine and UALCAN database. Survival analysis on LGG patients was then conducted based on age, gender, radiation therapy, histologic grade, tumor type and MTHFD2 expression. Cox regression analysis was also applied to predict the prognostic factor for overall survival (OS) of LGG. Finally, we performed enrichment analysis to reveal the potential MTHFD2-associated pathways involved in LGG. Results We found that MTHFD2 is highly expressed in LGG patients, and MTHFD2 expression is related with age, sub-types and TP53-mutation status (all P<0.05). Age, radiation therapy, histologic grade and tumor type were implicated in the survival of LGG patients (all P<0.05). High expression of MTHFD2 desirably improved the prognosis of LGG patients (P<0.001), especially for those patients with characteristics of age≥45 years old (P<0.001), receiving radiation therapy treatment (P=0.001), sub-type of astrocytoma and oligodendroglioma (all P<0.05), and histologic grade 3 (P<0.05). MTHFD2 was determined as an independent prognostic factor with age and grade for OS of LGG patients (all P<0.01). Pathway enrichment analysis indicated that MTHFD2 mainly participates in mTOR signaling pathway, apelin pathway and folate-mediated one-carbon metabolism.Conclusions The expression of MTHFD2 is associated with key clinical phenotype. High expression of MTHFD2 is favorable for the overall survival of LGG patients. MTHFD2 may serve as a novel prognostic biomarker and potential therapeutic target for LGG treatment.

scholarly journals The Expression of Tripartite Motif Protein 36 and β-Catenin Correlates with the Prognosis of Esophageal Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Hua Zhang ◽  
Wenlong Sun ◽  
Gaofeng Qiao ◽  
Bin Zhao ◽  
Xiangyan Liu ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Rank Test ◽  
Poor Overall Survival ◽  
Tripartite Motif ◽  
Tripartite Motif Protein ◽  
Low Expression

Aims. Tripartite motif protein 36 (TRIM36) plays a tumor-suppressive role in prostate cancer. However, there is little information on the clinical relevance of TRIM36 expression in esophageal cancer (ESCA). Methods. TRIM36 expression was analyzed by using The Cancer Genome Atlas (TCGA) ESCA dataset as well as by quantitative real-time polymerase chain reaction (PCR) and immunohistochemical (IHC) staining on samples from our hospital. Results. In the current study, the analysis of TCGA ESCA dataset suggested the decreased expression of TRIM36 in ESCA tissues. Further analyses on samples from our hospital demonstrated that TRIM36 was significantly downregulated in ESCA tissues than in the noncancerous controls at both the mRNA and protein levels. Moreover, gene set enrichment analysis on TCGA ESCA dataset suggested that TRIM36 expression was inversely correlated with the β-catenin pathway. IHC staining data showed that 66.25% (53/80) and 51.25% (41/80) of ESCA cases had a low expression of TRIM36 and a high expression of β-catenin, respectively. By Fisher’s exact test, we found that TRIM36 protein expression was significantly correlated with tumor size (P=0.0104), tumor stage (P=0.0169), lymph node metastasis (P=0.0021), vital status (P=0.0443), and β-catenin expression (P=0.0329). These findings suggest the potential clinical significance of TRIM36 in ESCA. Kaplan–Meier and log-rank test demonstrated that a low expression of TRIM6 and a high expression of β-catenin were associated with poor overall survival of ESCA patients. Conclusions. Our study provides evidence for the prognostic value of TRIM36 in ESCA.

scholarly journals Tumor mutational burden predicts survival in patients with low-grade gliomas expressing mutated IDH1

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Mahmoud S Alghamri ◽  
Rohit Thalla ◽  
Ruthvik P Avvari ◽  
Ali Dabaja ◽  
Ayman Taher ◽  
...  
Keyword(s):  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Low Grade ◽  
Low Grade Gliomas ◽  
Mutational Burden ◽  
Gene Sets ◽  
Tumor Mutational Burden ◽  
Cancer Genome Atlas ◽  
Gene Ontologies

Abstract Background Gliomas are the most common primary brain tumors. High-Grade Gliomas have a median survival (MS) of 18 months, while Low-Grade Gliomas (LGGs) have an MS of approximately 7.3 years. Seventy-six percent of patients with LGG express mutated isocitrate dehydrogenase (mIDH) enzyme. Survival of these patients ranges from 1 to 15 years, and tumor mutational burden ranges from 0.28 to 3.85 somatic mutations/megabase per tumor. We tested the hypothesis that the tumor mutational burden would predict the survival of patients with tumors bearing mIDH. Methods We analyzed the effect of tumor mutational burden on patients’ survival using clinical and genomic data of 1199 glioma patients from The Cancer Genome Atlas and validated our results using the Glioma Longitudinal AnalySiS consortium. Results High tumor mutational burden negatively correlates with the survival of patients with LGG harboring mIDH (P = .005). This effect was significant for both Oligodendroglioma (LGG-mIDH-O; MS = 2379 vs 4459 days in high vs low, respectively; P = .005) and Astrocytoma (LGG-mIDH-A; MS = 2286 vs 4412 days in high vs low respectively; P = .005). There was no differential representation of frequently mutated genes (eg, TP53, ATRX, CIC, and FUBP) in either group. Gene set enrichment analysis revealed an enrichment in Gene Ontologies related to cell cycle, DNA-damage response in high versus low tumor mutational burden. Finally, we identified 6 gene sets that predict survival for LGG-mIDH-A and LGG-mIDH-O. Conclusions we demonstrate that tumor mutational burden is a powerful, robust, and clinically relevant prognostic factor of MS in mIDH patients.

scholarly journals High SGO2 Expression Predicts Poor Overall Survival: A Potential Therapeutic Target for Hepatocellular Carcinoma

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 876
Author(s):  
Min Deng ◽  
Shaohua Li ◽  
Jie Mei ◽  
Wenping Lin ◽  
Jingwen Zou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Therapeutic Target ◽  
Tumor Grade ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Clinicopathological Parameters ◽  
Potential Therapeutic Target ◽  
Poor Overall Survival

Shugoshin2 (SGO2) may participate in the occurrence and development of tumors by regulating abnormal cell cycle division, but its prognostic value in hepatocellular carcinoma (HCC) remains unclear. In this study, we accessed The Cancer Genome Atlas (TCGA) database to get the clinical data and gene expression profile of HCC. The expression of SGO2 in HCC tissues and nontumor tissues and the relationship between SGO2 expression, survival, and clinicopathological parameters were analyzed. The SGO2 expression level was significantly higher in HCC tissues than in nontumor tissues (p < 0.001). An analysis from the Oncomine and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) databases also demonstrated that SGO2 was upregulated in HCC (all p < 0.001). A logistic regression analysis revealed that the high expression of SGO2 was significantly correlated with gender, tumor grade, pathological stage, T classification, and Eastern Cancer Oncology Group (ECOG) score (all p < 0.05). The overall survival (OS) of HCC patients with higher SGO2 expression was significantly poor (p < 0.001). A multivariate analysis showed that age and high expression of SGO2 were independent predictors of poor overall survival (all p < 0.05). Twelve signaling pathways were significantly enriched in samples with the high-SGO2 expression phenotype. Ten proteins and 34 genes were significantly correlated with SGO2. In conclusion, the expression of SGO2 is closely related to the survival of HCC. It may be used as a potential therapeutic target and prognostic marker of HCC.

scholarly journals Increased expression of homeobox 5 predicts poor prognosis: A potential therapeutic target for glioma

2021 ◽  
Author(s):  
Chengran Xu ◽  
Jinhai Huang ◽  
Yi Yang ◽  
Lun Li ◽  
Guangyu Li
Keyword(s):  
Cox Regression ◽  
Homeobox Gene ◽  
Enrichment Analysis ◽  
Tissue Expression ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Who Grade ◽  
Forecast Efficiency ◽  
Genome Atlas

Abstract Background: The homeobox gene 5 (HOXB5) encodes a transcription factor that regulates the central nervous system embryonic development. Of note, its expression pattern and prognostic role in glioma remain unelucidated. This study aimed to identify the relationship between HOXB5 and glioma by investigating the HOXB5 expression data from the The Cancer Genome Atlas (TCGA) and The Genotype Tissue Expression (GTEx) databases and validating the obtained data using the Chinese Glioma Genome Atlas (CGGA) database. Kaplan-Meier and univariate cox regression analyses were performed to assess the prognostic value of HOXB5. The key functions and signaling pathways of HOXB5 were analyzed using GSEA and GSVA. Immune infiltration was calculated using Microenvironment Cell Populations-counter (MCP-counter), single-sample Gene Set Enrichment Analysis (ssGSEA), and ESTIMATE algorithms.Result: HOXB5 expression was elevated in glioma tissues. The increased levels of HOXB5 were significantly correlated with a higher WHO grade and aggressive cancer phenotypes. HOXB5 overexpression represented a risk factor that was associated with shorter overall survival (OS) while exhibiting a moderate forecast efficiency in most clinical subgroups. These results were validated using the CGGA and Rembrandt datasets. Furthermore, the functional analysis showed enrichment of angiogenesis, the IL6/JAK-STAT3 pathway, and inflammatory response in the tissues that showed high expression of HOXB5. Lastly, the high expression of HOXB5 was associated with enrichment of Tregs and MDSCs, and HOXB5 expression was shown to play a role in several immune checkpoint genes.Conclusions: HOXB5 may serve as a predictive factor of glioma malignancy and prognostic status and represents potential as a molecular treatment candidate.

scholarly journals Validation of the Functions and Prognostic Values of Synapse Associated Proteins in Lower-Grade Glioma

2020 ◽  
Author(s):  
Han Lin ◽  
Yong Yang ◽  
Chongxian Hou ◽  
Jiantao Zheng ◽  
Guangzhao Lv ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Prognostic Models ◽  
Normal Brain ◽  
Lower Grade ◽  
Associated Proteins ◽  
Genome Atlas

Abstract BackgroundSynapse and synapse associated proteins (SAPs) play critical roles in various neurodegeneration diseases and brain tumors. However, in lower-grade gliomas (LGG), SAPs have not been explored systematically. Herein, we are going to explore SAPs expression profile and its clinicopathological significance in LGG which can offer new insights to glioma therapy. MethodIn this study, we used five sources including, Venkatesh, Shen, Colón, Jüttner R, Gene Ontology (GO) project to integrate a list of SAPs that covered 231 proteins with synaptogenesis activity and post synapse formation. The LGG RNA-seq data were downloaded from gene expression omnibus (GEO) database, The Cancer Genome Atlas (TCGA), and Chinese Glioma Genome Atlas (CGGA). The differentially expressed SAPs were filtered out and constructed PPI to search for key modules and SAPs. Then, using Kaplan–Meier survival analysis, least absolute shrinkage and selection operator (LASSO), and multicox regression analysis, the prognostic significance of these key SAPs was evaluated. CGGA database, Human Protein Altas (HPA) and quantitative real-time PCR were used to verify our findings. ResultData from function enrichment analysis revealed functions of differentially expressed SAPs in synapse organization and glutamatergic receptor pathway in LGGs. Survival analysis revealed four SAPs, GRIK2, GABRD, GRID2, ARC that were correlate with the prognosis of LGG patients and used to construct the prognostic models. Among them, the expression of GABRD was lower in glioma tissue than normal brain tissue, but higher in seizure LGG patients than non-seizure patients. The four-SAPs signature was revealed as an independent prognostic factor in gliomas. ConclusionOur study presented a novel strategy to assess the prognostic risks of LGGs, based on the expression of SAPs. Also, we revealed that several SAPs upregulated in patients with seizures, indicating that they are linked to the pathogenesis of seizures in glioma patients.

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