Prognostic Value and Therapeutic Perspectives of CXCR Members in the Glioma Microenvironment

He, Jiarong; Jiang, Zhongzhong; Lei, Jiawei; Zhou, Wen; Cui, Yan; Luo, Biao; Zhang, Mingming

doi:10.3389/fgene.2022.787141

Cited by 3 publications

(5 citation statements)

References 34 publications

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“…We found that CXCR4 is closely related to the prognosis of patients with GBM and preliminarily verified that CXCR4 is an important index to judge the prognosis of patients with GBM. Our previous study found that the prognosis of GBM with high expression of CXCR4 was worse, which was consistent with that reported in the literature [ 26 ]. Secondly, based on t-ROC and DCA to build a high-precision GBM prognosis prediction model to verify its application value in GBM patients.…”

Section: Discussionsupporting

confidence: 92%

“…A growing number of studies have shown that the CXCR members are frequently involved in tumorigenesis and development and play an essential role in antitumor immunity [ 25 , 26 ]. However, the clinical value and application of the CXCR members in primary GBM has not been thoroughly clarified.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have suggested that CXCR1/2/3/4/7 may play a crucial role in gliomas, and have a significant impact on overall glioma survival [ 26 ]. It was confirmed that CXCR5 is not associated with glioma prognosis, which is consistent with the results of our present study.…”

Section: Discussionmentioning

confidence: 99%

“…It was confirmed that CXCR5 is not associated with glioma prognosis, which is consistent with the results of our present study. In addition, previous studies elaborated that CXCR6 expression in GBM and normal brain tissue is not significantly different [ 26 ]. This is consistent with our validation results in TCGA, but the CXCR6 expression is significantly different in CGGA.…”

Section: Discussionmentioning

confidence: 99%

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Development and Validation of CXCR4 Nomogram-Based Immune Infiltration/Tumor Inflammation in Primary Glioblastoma

et al. 2023

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Glioblastoma (GBM) is a highly malignant and aggressive tumor with poor prognosis. Therefore, the discovery of new prognostic molecular markers is of great significance for clinical prognosis. The CXC chemokine receptor (CXCR) members play a key regulatory role in many cancers. In this study, we explore the clinical value and application of the CXCR members in primary glioblastoma. Two GBM datasets from The Cancer Genome Atlas (TCGA) and The China Glioma Genome Atlas (CGGA) databases were used to explore the relationship between differential expression of CXCRs and GBM subtypes as well as immune infiltration. C-X-C motif chemokine receptor 4 (CXCR4) was screened as an independent prognostic factor, and a nomogram and risk prediction model were developed and tested in the CGGA database using the TCGA database. Receiver operating curve (ROC) and decision curve analysis (DCA) found good accuracy and net benefit of the models. The correlation of CXCR4 with immune infiltration and tumor was analyzed using CancerSEA and TIMER. In in vitro experiments, we found that CXCR4 was significantly overexpressed in glioblastoma and was closely related to the inflammatory response of U251/U87 cells. CXCR4 is an excellent independent prognostic factor for glioblastoma and positively correlates with tumor inflammation.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Development and Validation of CXCR4 Nomogram-Based Immune Infiltration/Tumor Inflammation in Primary Glioblastoma

et al. 2023

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“…Furthermore, neutrophil can stimulate dormant cancer cells through release of MMP9 which can produce epitopes that bind to tumor integrins and trigger the proliferation of cancer cells [26,27]. It has been reported that CXCR1 mRNA expression is significantly higher in patients with glioma than in normal individuals [64]. The tumor-promoting activity of neutrophils was related to growth factors and chemotactic factors [53,65,66], and CXCR was involved in promoting neutrophil maturation, survival, and recruitment [18,[67][68][69].…”

Section: Discussionmentioning

confidence: 99%

The prognostic significance of tumor-associated neutrophils and circulating neutrophils in glioblastoma (WHO CNS5 classification)

Wang

et al. 2023

BMC Cancer

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Background Tumor-associated neutrophils (TANs) in the tumor microenvironment are prognostic biomarkers in many malignancies. However, it is unclear whether TANs can serve as a prognostic marker for clinical outcomes in patients with glioblastoma (GBM), as classified according to World Health Organization Classification of Tumors of the Central Nervous System, fifth edition (CNS5). In the present study, we analyzed correlations of TANs and peripheral blood neutrophils prior to radiotherapy with overall survival (OS) in GBM (CNS5). Methods RNA-seq expression profiles of patients with newly diagnosed GBM (CNS5) were extracted from The Cancer Genome Atlas (TCGA), and The Chinese Glioma Genome Atlas (CGGA). TAN infiltration was inferred using CIBERSORTx algorithm. Neutrophil counts prior to radiotherapy in newly diagnosed GBM (CNS5) were obtained from the First Affiliated Hospital of Fujian Medical University. The prognostic value of TANs and peripheral blood neutrophils before radiotherapy was investigated using Kaplan-Meier analysis and Cox proportional hazards models. The robustness of these findings was evaluated by sensitivity analysis, and E values were calculated. Results A total of 146 and 173 individuals with GBM (CNS5) were identified from the TCGA and CGGA cohorts, respectively. High infiltration of TANs was of prognostic of poor OS in TCGA (HR = 1.621, 95% CI: 1.004–2.619) and CGGA (HR = 1.546, 95% CI: 1.029–2.323). Levels of peripheral blood neutrophils before radiotherapy (HR = 2.073, 95% CI: 1.077–3.990) were independently associated with poor prognosis. Sensitivity analysis determined that the E-value of high TANs infiltration was 2.140 and 2.465 in the TCGA and CGGA cohorts. Conclusions TANs and peripheral blood neutrophil levels before radiotherapy are prognostic of poor outcomes in GBM (CNS5).

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Construction and validation of an angiogenesis-related gene expression signature associated with clinical outcome and tumor immune microenvironment in glioma

Wang

et al. 2022

Front. Genet.

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Background: Glioma is the most prevalent malignant intracranial tumor. Many studies have shown that angiogenesis plays a crucial role in glioma tumorigenesis, metastasis, and prognosis. In this study, we conducted a comprehensive analysis of angiogenesis-related genes (ARGs) in glioma.Methods: RNA-sequencing data of glioma patients were obtained from TCGA and CGGA databases. Via consensus clustering analysis, ARGs in the sequencing data were distinctly classified into two subgroups. We performed univariate Cox regression analysis to determine prognostic differentially expressed ARGs and least absolute shrinkage and selection operator Cox regression to construct a 14-ARG risk signature. The CIBERSORT algorithm was used to explore immune cell infiltration, and the ESTIMATE algorithm was applied to calculate immune and stromal scores.Results: We found that the 14-ARG signature reflected the infiltration characteristics of different immune cells in the tumor immune microenvironment. Additionally, total tumor mutational burden increased significantly in the high-risk group. We combined the 14-ARG signature with patient clinicopathological data to construct a nomogram for predicting 1-, 3-, and 5-year overall survival with good accuracy. The predictive value of the prognostic model was verified in the CGGA cohort. SPP1 was a potential biomarker of glioma risk and was involved in the proliferation, invasion, and angiogenesis of glioma cells.Conclusion: In conclusion, we established and validated a novel ARG risk signature that independently predicted the clinical outcomes of glioma patients and was associated with the tumor immune microenvironment.

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Prognostic Value and Therapeutic Perspectives of CXCR Members in the Glioma Microenvironment

Cited by 3 publications

References 34 publications

Development and Validation of CXCR4 Nomogram-Based Immune Infiltration/Tumor Inflammation in Primary Glioblastoma

Development and Validation of CXCR4 Nomogram-Based Immune Infiltration/Tumor Inflammation in Primary Glioblastoma

The prognostic significance of tumor-associated neutrophils and circulating neutrophils in glioblastoma (WHO CNS5 classification)

Construction and validation of an angiogenesis-related gene expression signature associated with clinical outcome and tumor immune microenvironment in glioma

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