Polymorphisms in IL-4/IL-13 pathway genes and glioma risk: an updated meta-analysis

Chen, Peiqin; Chen, Chao; Chen, Kun; Xu, Tao; Luo, Chun

doi:10.1007/s13277-014-2895-8

Cited by 9 publications

(7 citation statements)

References 37 publications

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“…Then, the new WHO classification published in 2021 included more molecular biomarkers [ 25 ]. Since then, a diverse set of biomarkers have been implicated as prognostic indicators in gliomas, including checkpoint molecules (PD-1, CTLA-4, TIM-3) [ 26 , 27 , 28 ], growth/angiogenesis proteins (EGFR) [ 29 ], and cytokines (TGF-β, IL-4, IL-13) [ 30 , 31 ]. Among them, the effects of IL-4/IL-4 receptors were investigated in the last decade [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of an IL-4-Related Gene Risk Signature for Malignancy, Prognosis and Immune Phenotype Prediction in Glioma

Yang

Tang

et al. 2022

Brain Sciences

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Background: Emerging molecular and genetic biomarkers have been introduced to classify gliomas in the past decades. Here, we introduced a risk signature based on the cellular response to the IL-4 gene set through Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Methods: In this study, we provide a bioinformatic profiling of our risk signature for the malignancy, prognosis and immune phenotype of glioma. A cohort of 325 patients with whole genome RNA-seq expression data from the Chinese Glioma Genome Atlas (CGGA) dataset was used as the training set, while another cohort of 667 patients from The Cancer Genome Atlas (TCGA) dataset was used as the validating set. The LASSO model identified a 10-gene signature which was considered as the optimal model. Results: The signature was confirmed to be a good predictor of clinical and molecular features involved in the malignancy of gliomas. We also identified that our risk signature could serve as an independently prognostic biomarker in patients with gliomas (p < 0.0001). Correlation analysis showed that our risk signature was strongly correlated with the Tregs, M0 macrophages and NK cells infiltrated in the microenvironment of glioma, which might be a supplement to the existing incomplete innate immune mechanism of glioma phenotypes. Conclusions: Our IL-4-related gene signature was associated with more aggressive and immunosuppressive phenotypes of gliomas. The risk score could predict prognosis independently in glioma, which might provide a new insight for understanding the IL-4 involved mechanism of gliomas.

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Section: Discussionmentioning

confidence: 99%

Identification of an IL-4-Related Gene Risk Signature for Malignancy, Prognosis and Immune Phenotype Prediction in Glioma

Yang

Tang

et al. 2022

Brain Sciences

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“…Moreover, stratification by source of control did not substantially reduce the heterogeneity in the subgroups, suggesting that ethnicity and source of control did not fully explain the heterogeneity among studies. Two previous meta-analyses have analyzed the association between IL-13 gene rs20541 polymorphism and glioma susceptibility [6,19]. For the study by Chen et al [19], only the recessive model was assessed, and no association was found.…”

Section: Discussionmentioning

confidence: 99%

“…Two previous meta-analyses have analyzed the association between IL-13 gene rs20541 polymorphism and glioma susceptibility [6,19]. For the study by Chen et al [19], only the recessive model was assessed, and no association was found. In this study, the rs1800925 polymorphism was also tested with the susceptibility to glioma, but still no association was found.…”

Section: Discussionmentioning

confidence: 99%

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Association between <b><i>IL-13</i></b> Gene rs20541 Polymorphism and Glioma Susceptibility: A Meta-Analysis

Yang

Yuan²,

Zhang³

et al. 2018

Oncol Res Treat

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Objective: We performed a meta-analysis to estimate the association between IL-13 gene rs20541 (R130Q) polymorphism and the susceptibility of glioma. Patients and Methods: Potentially eligible studies published before February 1, 2016 were searched in 4 databases including PubMed, EMBASE, EBSCO, and Ovid. Odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were used to estimate the strength of relationship between the IL-13 gene rs20541 polymorphism and glioma susceptibility. Stata 11.0 software was used to perform the present meta-analysis. Results: In total, 10 case-control studies with 13 datasets including 3,123 cases and 5,390 controls were identified. A significant increase in glioma susceptibility was found in the dominant model (AA + AG vs. GG: OR = 1.14, 95% CI 1.01-1.29; P = 0.031). Significantly decreasing glioma susceptibility was found for Asians in the heterozygote comparison (AG vs. GG: OR = 0.74, 95% CI 0.55-0.99; P = 0.042) and the allele contrast genetic model (A vs. G: OR = 0.67, 95% CI 0.47-0.96; P = 0.028). By contrast, in Caucasians, a significant increase in glioma susceptibility was found in the dominant model (AA + AG vs. GG: OR = 1.25, 95% CI 1.11-1.41; P = 0.000). Conclusion: There may be a weak association between the IL-13 gene rs20541 polymorphism and glioma susceptibility, and the associations may be different between ethnicities.

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“…In addition, the existing IL-4R was closely related to tumor genesis by numerous mechanisms [ 25 ]. For example, the polymorphisms in the interleukin (IL)-4/IL-13 pathway was reported previously to be associated with glioma [ 27 ]. Therefore, IL-4R-based tumor targeting drug delivery could be used for the treatment of several tumors.…”

Section: Introductionmentioning

confidence: 99%

Application of dual targeting drug delivery system for the improvement of anti-glioma efficacy of doxorubicin

et al. 2017

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Chemotherapy of glioma is always hampered by the unsatisfactory tumor accumulation of drugs, of which the most noticeable obstacle is the limited drug permeability from vessels into tumor inner. In the present study, we developed a novel nanocarrier for the delivery of doxorubicin to brain tumor. Such novel drug delivery system was mainly composed of a tumor homing peptide and DOX-loaded PLA nanoparticles (AP1-NP-DOX). CRKRLDRNC peptide, named as AP1, was a newly glioma affinity peptide which could specifically binds to interleukin-4 receptor (IL-4R), highly expressing on both glioma cells and angiogenesis. Our findings showed that the peptide-functionalized nanoparticles had a high affinity with both tumor cells and vascular endothelial cells. Besides, tumor targeting assay exhibited that AP1 decorated nanoparticles accumulated more in tumor site than the unmodified ones. Moreover, the results of tumor uptake experiments indicated that AP1-NP-DOX might own the ability of blood brain barrier (BBB) penetration. In the anti-glioma study, AP1-NP-DOX exhibited the highest therapeutic effect on tumor-bearing mice compared with the unmodified nanoparticles and free doxorubicin. These results together indicated that AP1-functionalized nanoparticles could represent a promising way to expand the treatment horizons of onco-therapy.

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Polymorphisms in IL-4/IL-13 pathway genes and glioma risk: an updated meta-analysis

Cited by 9 publications

References 37 publications

Identification of an IL-4-Related Gene Risk Signature for Malignancy, Prognosis and Immune Phenotype Prediction in Glioma

Identification of an IL-4-Related Gene Risk Signature for Malignancy, Prognosis and Immune Phenotype Prediction in Glioma

Association between <b><i>IL-13</i></b> Gene rs20541 Polymorphism and Glioma Susceptibility: A Meta-Analysis

Application of dual targeting drug delivery system for the improvement of anti-glioma efficacy of doxorubicin

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