Interferon-Stimulated Exonuclease Gene 20 is A Prognosis and Predictive Biomarker and Correlated with Macrophages M2 Polarization in Glioblastoma: A Pan-Cancer Analysis

Abstract Background: Since the mutation of isocitrate dehydrogenase 1 was confirmed to be different in the tumor microenvironment of multiple cancer types, several researchers have included it in the study of tumor-infiltrating immune cells. Interferon-stimulated exonuclease gene 20 (ISG20) plays a role in the modulation of immunity and inflammation, and its abnormally high expression is conducive for the progression of tumor malignancy. However, whether ISG20 is associated with isocitrate dehydrogenase 1 mutation during tumorigenesis and cancer progression remains unknown to date. Methods: TIMER2.0, ONCOMINE, GEPIA2, TCGA and CGGA were applied to assess the clinical significance of ISG20 and its correlation with tumor-infiltrating immune cells in glioma. cBioPortal and MethSurv databases were used to observe the genetic and DNA methylation changes of ISG20, respectively. Visualization of data was mostly achieved by R language. Quantitative real-time PCR (qRT-PCR) and Immunohistochemistry (IHC) was performed to evaluate the mRNA and protein expression.Results: ISG20 expression was significantly different in most cancers. However, when we combined ISG20 with isocitrate dehydrogenase 1 mutation, we found significant differences only in glioblastoma (GBM). The clinical values of ISG20 in glioblastoma showed that the ISG20 overexpression was strongly associated with a worse overall survival (OS). Additionally, ISG20 was altered in 9% of samples of patients with GBM, and ISG20 expression was negatively correlated with its DNA methylation level. More importantly, ISG20 expression was associated with macrophage alternatively activated (M2) polarization in glioblastoma. Conclusions: ISG20 overexpression is conducive to malignant phenotype but adverse to OS, suggesting that ISG20 is a potential therapeutic target and prognosis and predictive biomarker in patients with GBM.

Download Full-text

Faculty Opinions recommendation of Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13411032.14782156 ◽

2011 ◽

Author(s):

Lewis Cantley

Keyword(s):

Isocitrate Dehydrogenase ◽

Acute Myelogenous Leukemia ◽

Myelogenous Leukemia ◽

Isocitrate Dehydrogenase 1 ◽

Acute Myelogenous

Download Full-text

Dual‐Knockout of Mutant Isocitrate Dehydrogenase 1 and 2 Subtypes towards Glioma Therapy: Structural Mechanistic insights on the role of Vorasidenib

Chemistry & Biodiversity ◽

10.1002/cbdv.202100110 ◽

2021 ◽

Author(s):

Preantha Poonan ◽

Clement Agoni ◽

Mahmoud Soliman

Keyword(s):

Isocitrate Dehydrogenase ◽

Isocitrate Dehydrogenase 1

Download Full-text

PD65-12 THE ANDROGEN RECEPTOR BECOMES A NOVEL PREDICTIVE BIOMARKER OF PROSTATE CANCER PROGRESSION WHEN POST TRANSLATIONALLY ACTIVATED BY THE FER KINASE ON TYROSINE 223

The Journal of Urology ◽

10.1016/j.juro.2017.02.2962 ◽

2017 ◽

Vol 197 (4S) ◽

Author(s):

Turki Altaylouni ◽

Fatima Zouanat ◽

Eleonora Scarlata ◽

Tarik Benidir ◽

Lucie Hamel ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Cancer Progression ◽

Predictive Biomarker ◽

Prostate Cancer Progression

Download Full-text

Structural analysis of oncogenic mutation of isocitrate dehydrogenase 1

Molecular BioSystems ◽

10.1039/c6mb00182c ◽

2016 ◽

Vol 12 (7) ◽

pp. 2276-2287 ◽

Cited By ~ 56

Author(s):

Vidya Rajendran

Keyword(s):

Structural Analysis ◽

Isocitrate Dehydrogenase ◽

Isocitrate Dehydrogenase 1 ◽

Oncogenic Mutation

Arginine to histidine mutation at position 132 (R132H) in isocitrate dehydrogenase 1 (IDH1) led to reduced affinity of the respective enzymes for isocitrate and increased affinity for α-ketoglutarate (AKG) and NADPH.

Download Full-text

Detection of 2-hydroxyglutaric acid in vivo by proton magnetic resonance spectroscopy in U87 glioma cells overexpressing isocitrate dehydrogenase-1 mutation

Neuro-Oncology ◽

10.1093/neuonc/nos258 ◽

2012 ◽

Vol 14 (12) ◽

pp. 1465-1472 ◽

Cited By ~ 29

Author(s):

J. Lazovic ◽

H. Soto ◽

D. Piccioni ◽

J. R. Lo Ru ◽

S. Li ◽

...

Keyword(s):

Magnetic Resonance ◽

Magnetic Resonance Spectroscopy ◽

Isocitrate Dehydrogenase ◽

Proton Magnetic Resonance ◽

Proton Magnetic Resonance Spectroscopy ◽

Glioma Cells ◽

Resonance Spectroscopy ◽

Isocitrate Dehydrogenase 1 ◽

Hydroxyglutaric Acid

Download Full-text

Gene expression and DNA methylation analyses suggest that two immune related genes are prognostic factors of colorectal cancer

BMC Medical Genomics ◽

10.1186/s12920-021-00966-3 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Xiao-Liang Xing ◽

Zhi-Yong Yao ◽

Chaoqun Xing ◽

Zhi Huang ◽

Jing Peng ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Risk Assessment ◽

Dna Methylation ◽

Differentially Expressed Genes ◽

Risk Score ◽

Immune Cells ◽

Assessment Model ◽

Differentially Expressed ◽

Risk Assessment Model

Abstract Background Colorectal cancer (CRC) is the second most prevalent cancer, as it accounts for approximately 10% of all annually diagnosed cancers. Studies have indicated that DNA methylation is involved in cancer genesis. The purpose of this study was to investigate the relationships among DNA methylation, gene expression and the tumor-immune microenvironment of CRC, and finally, to identify potential key genes related to immune cell infiltration in CRC. Methods In the present study, we used the ChAMP and DESeq2 packages, correlation analyses, and Cox regression analyses to identify immune-related differentially expressed genes (IR-DEGs) that were correlated with aberrant methylation and to construct a risk assessment model. Results Finally, we found that HSPA1A expression and CCRL2 expression were positively and negatively associated with the risk score of CRC, respectively. Patients in the high-risk group were more positively correlated with some types of tumor-infiltrating immune cells, whereas they were negatively correlated with other tumor-infiltrating immune cells. After the patients were regrouped according to the median risk score, we could more effectively distinguish them based on survival outcome, clinicopathological characteristics, specific tumor-immune infiltration status and highly expressed immune-related biomarkers. Conclusion This study suggested that the risk assessment model constructed by pairing immune-related differentially expressed genes correlated with aberrant DNA methylation could predict the outcome of CRC patients and might help to identify those patients who could benefit from antitumor immunotherapy.

Download Full-text

Circ-GALNT16 Restrains Colorectal Cancer Progression by Enhancing the SUMOylation of hnRNPK

10.21203/rs.3.rs-501100/v1 ◽

2021 ◽

Author(s):

Chaofan Peng ◽

Yuqian Tan ◽

Peng Yang ◽

Kangpeng Jin ◽

Chuan Zhang ◽

...

Keyword(s):

Colorectal Cancer ◽

Dna Binding ◽

Rna Sequencing ◽

Cancer Progression ◽

Molecular Mechanisms ◽

Transcriptional Level ◽

Multiple Cancer ◽

Binding Ability ◽

Colorectal Cancer Progression

Abstract BackgroundEmerging studies have investigated circRNAs as significant regulation factors in multiple cancer progression. Nevertheless, the biological functions and underlying mechanisms of circRNAs in colorectal cancer progression remain unclear.MethodsA novel circRNA (circ-GALNT16) was identified by microarray and qRT-PCR. A series of phenotype experiments in vitro and vivo were performed to investigate the role of circ-GALNT16 in CRC. FISH, RNA pulldown assay, RIP assay, RNA sequencing, coimmunoprecipitation, and ChIP were constructed to explore the molecular mechanisms of circ-GALNT16 in colorectal cancer.ResultsCirc-GALNT16 was downregulated in colorectal cancer and negatively correlated with poor prognosis. Circ-GALNT16 suppressed the proliferation and metastasis ability of colorectal cancer in vitro and vivo. Mechanistically, circ-GALNT16 could bind to the KH3 domain of heterogeneous nuclear ribonucleoprotein K (hnRNPK), which resulted in the SUMOylation of hnRNPK. Additionally, circ-GALNT16 could enhance the hnRNPK-p53 complex by facilitating the SUMOylation of hnRNPK. Furthermore, RNA sequencing assay identified serpin family E member 1 as the target gene of circ-GALNT16 at the transcriptional level. Rescue assays revealed that circ-GALNT16 regulated the expression of Serpine1 by inhibiting the deSUMOylation of hnRNPK mediated by SUMO specific peptidase 2 and then regulating the sequence-specific DNA binding ability of the hnRNPK-p53 transcriptional complex.ConclusionsCirc-GALNT16 suppressed CRC progression via inhibiting Serpine1 expression through adjusting the sequence-specific DNA binding ability of the SENP2-mediated hnRNPK-p53 transcriptional complex and might work as a biomarker and therapeutic target for CRC.

Download Full-text