BACKGROUND AND PURPOSE: Previous studies have suggested that increased mortality and disability in patients with brain tumor are associated with peritumoral brain edema. However, the mechanism of peritumoral brain edema in brain tumors is unknown. This study aimed to investigate the effect of Piezo1 overexpression on peritumoral brain edema in glioblastomas. MATERIALS AND METHODS: The Piezo1 expression in cell lines and paired samples was detected by quantitative reverse transcription polymerase chain reaction, Western blot, and immunohistochemistry. Sixty-four patients with glioblastomas were analyzed retrospectively. The Piezo1 expression of tumor tissue was detected by immunohistochemistry. The diameters of tumor and edema were measured by preoperative MR imaging, and the edema index value was calculated. RESULTS: Western blot and quantitative reverse transcription polymerase chain reaction showed that Piezo1 expression was higher in 6 glioma cell lines than in the normal astrocyte cell line. Compared with peritumoral tissues, Piezo1 was up-regulated in tumor tissues. Sixty-four patients with glioblastomas were enrolled in further study. Piezo1 was higher in the moderate edema group than in the mild edema group (P , .001), higher in the severe edema group than in the moderate edema group (P , .001), and correlated with the edema index (r ¼ 0.73; P , .001). Receiver operating characteristic curve analysis showed that the edema index yielded an area under the curve of 0.867 (95% CI, 0.76-0.97; P , .001), with a sensitivity of 100% and a specificity of 70%. CONCLUSIONS: Piezo1 overexpression is positively correlated with the degree of peritumoral brain edema in glioblastomas. Predicting high Piezo1 expression in tumor tissues based on the edema extent shows good sensitivity and specificity. ABBREVIATIONS: EI ¼ edema index; GBM ¼ glioblastoma; IHC ¼ immunohistochemistry; IRS ¼ immunoreactivity score; PTBE ¼ peritumoral brain edema; qRT-PCR ¼ quantitative reverse transcription polymerase chain reaction; ROC ¼ receiver operating characteristic; WHO ¼ World Health Organization
Background: Previous studies have reported the critical roles of tumor cells and the tumor microenvironment in tumor prognosis and immunotherapeutic response. However, how Tenascin-XB (TNXB) expression relates to glioma prognosis and to the levels of tumor-infiltrating immune cells in various cancers has remained elusive. Therefore, this work aimed to investigate the expression, prognostic value, biological function and correlation between TNXB expression and the levels of tumor-infiltrating immune cells in glioma tissues.Methods: First, we explored TNXB expression in glioma tissues by using online biological databases. Second, we assessed the clinical importance of TNXB expression with chi-squared tests, Cox regression and Kaplan-Meier curve analyses. Third, we examined the relationship between TNXB expression and the levels of tumor-infiltrating immune cells in glioma tissues in an online database. Additionally, we assessed the associations of TNXB expression with genetic markers of immune cells and common immune-checkpoint molecules.Results: Elevated TNXB expression in glioma tissues correlated with tumor grade, according to several databases. Elevated TNXB expression was significantly associated with negative clinicopathological manifestations and poorer prognosis, on the basis of TCGA (n=510) data. Furthermore, univariate and multivariate Cox regression indicated that TNXB was an independent indicator of glioma prognosis. Pathway enrichment analyses suggested that TNXB participates in the immune response, humoral immune response and interferon-gamma-mediated signaling pathways. Importantly, TNXB expression was significantly associated with higher levels of tumor-infiltrating immune cells in diverse cancers. Furthermore, TNXB expression was strongly associated with genetic markers of immune cells and common immune-checkpoint molecules (e.g., PD-1, PD-L1, CTLA4, TIM-3, LAG3, PDCD1LG2, TIGIT and Siglec-15).Conclusions: TNXB expression correlates with poorer prognosis and higher levels of tumor-infiltrating immune cells in several cancers. In addition, TNXB expression is likely to contribute to the regulation of dendritic cells, exhausted T cells, regulatory T cells and tumor-associated macrophages in gliomas. Consequently, TNXB may serve as an important prognostic marker and may play an immunomodulatory role in tumors.
Background C5AR2 is recognized as a proinflammatory molecule and activates the inflammatory response in multiple disorders. However, little has been reported on C5AR2 in glioma. This study sought to explore its expression, biological function, and association with clinical pathological indicators, prognosis, and immune infiltration levels in glioma through glioma cohorts. Methods A cohort of 657 patients was screened from the Chinese Glioma Genome Atlas (CGGA). χ2 test was performed to calculate the difference of classified variables. Cox proportional hazard regression modeling was used to identify independent prognostic indicators of glioma patients. A survival plot was generated by the Kaplan–Meier method. The immune cell infiltration score of glioma patients was calculated by TIMER algorithm. Results We observed that high expression of C5AR2 was strongly associated with malignant clinical indicators in 657 patients with glioma, and patients with high C5AR2 expression had worse prognoses. Multivariate Cox analysis showed that C5AR2 could be a new independent prognostic indicator for glioma patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that C5AR2 overexpression correlated with multiple inflammatory and immune biological processes. Additionally, high C5AR2 expression was strongly associated with higher abundance and marker gene expression of multiple tumor immune cells in low‐grade glioma. Finally, a model was constructed to improve the prognostic evaluation of glioma patients. Conclusions The C5AR2 gene is highly expressed in gliomas and is significantly associated with clinical indicators of malignant progression in glioma patients. In glioma, patients with high C5AR2 expression displayed a worse outcome. In glioma tissues, the expression level of C5AR2 highly correlated with the abundance of tumor immune cell infiltration. Additionally, GO and KEGG enrichment analysis revealed that C5AR2 expression may be involved in a variety of immune and inflammatory biological processes.
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