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Increased M1 Macrophages Infiltration Correlated With Poor Survival Outcomes and Radiation Response in Gliomas.

ABSTRACT: Background:Gliomas are the malignance of a poor prognosis. The current WHO classification remains unable to predict survival outcomes accurately. Novel surrogates are highly required for improved stratification of patients and hence, allowing to delivery of the most appropriate treatment. Methods:Transcriptional profiles of 301 glioma cases on the platform of Chinese Glioma Genome Atlas (CGGA) were retrospectively studied. Results:Extracellular matrix (ECM) scores were established by integrating a panel of most featured gene-signatures, correlating well with pathological tumor stages. Linear regression analysis revealed that the ECM score corroborated with the infiltration status of monocytes, M0 and M1 macrophages. Furthermore, the WHO stage II-IV dependent abundance of those 3 immune cells was determined. Univariate and multivariate analysis of clinicopathological characteristics in the GBM cohort identified M1 enrichment score as an independent risk factor. A high abundance of M1 macrophages was associated with poor survival outcomes and radiotherapy response in IDH-wildtype GBM. Conclusions:Our study demonstrated that M1 macrophages correlated with WHO grades and predicted robustly for the survival performance for GBM patients. Increased infiltration of M1 macrophages was associated with a poor radiation response for IDH-wildtype GBM. Together, it will facilitate more precise stratifications of glioma patients based on molecular and immunological surrogates.

SUBMITTER: Zhou Z

PROVIDER: S-EPMC7573741 | biostudies-literature | 2020 Oct-Dec

REPOSITORIES: biostudies-literature

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Increased M1 Macrophages Infiltration Correlated With Poor Survival Outcomes and Radiation Response in Gliomas.

Zhou Zhaoming Z Wen Lei L Lai Mingyao M Shan Changguo C Wang Jian J Wang Rong R Li Hainan H Chen Longhua L Cai Linbo L Zhou Meijuan M Zhou Cheng C

Dose-response : a publication of International Hormesis Society 20201016 4

<h4>Background</h4>Gliomas are the malignance of a poor prognosis. The current WHO classification remains unable to predict survival outcomes accurately. Novel surrogates are highly required for improved stratification of patients and hence, allowing to delivery of the most appropriate treatment.<h4>Methods</h4>Transcriptional profiles of 301 glioma cases on the platform of Chinese Glioma Genome Atlas (CGGA) were retrospectively studied.<h4>Results</h4>Extracellular matrix (ECM) scores were esta ...[more]

PMID: 33117094

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Project description:Background: Glioma, the most common brain tumor, is a heterogeneous group of glia-derived tumors, the majority of which have characteristics of diffuse infiltration and immunosuppression. The LGALS protein family is a large class of sugar-binding proteins. Among them, LGALS3 has been reported to promote tumor development and progression in some cancers. However, the clinical significance and biological functions of LGALS3 in glioma remain virtually unknown. The purpose of our research is to detect LGALS3 expression and its prognostic value in glioma and reveal the relationship between its expression and the clinico/molecular-pathological features of patients and immune cell infiltration. Methods: LGALS3 protein expression was examined by immunohistochemistry. The mRNA expression data of LGALS3 was downloaded and analyzed from TCGA and Rembrandt datasets. The association between LGALS3 and glioma clinically relevant diagnostic/molecular markers (IDH, 1p19q, ATRX, MGMT, and TERT) was examined using the Chi-Squared (χ2) test. The correlation between LGALS3 expression and the infiltration of multiple intra-tumoral immune cell types, including B cells (CD20), T cells (CD4 and CD8), macrophages (CD68), and M2 tumor-associated macrophages (CD163), was evaluated by Spearman correlation analysis. Kaplan-Meier analysis and the Cox regression analysis were applied to evaluate the prognostic value of LGALS3 in glioma. The log-rank test was used to evaluate Kaplan-Meier results for significance. Results: Out of all 304 glioma cases, LGALS3 protein was expressed in 125 glioma cases (41.1%, 125/304), with 69.2% (9/13) in WHO I, 9.8% (8/82) in WHO II, 34.2% (26/76) in WHO III, and 61.7% (82/133) in WHO IV. The expression of LGALS3 was correlated with patient age, WHO grade, PHH3 (mitosis), Ki67 index, IDH, 1p/19q codeletion, and TERT promoter status. LGALS3 was an independent poor prognostic marker in diffusely infiltrating gliomas and was positively correlated with immune cell infiltration, particularly CD163+ tumor-associated macrophages in the TCGA dataset, Rembrandt dataset, and our SYSUCC cohort (R = 0.419, 0.627, and 0.724). Conclusion: LGALS3 was highly expressed in pilocytic astrocytoma, GBM, and IDH wild-type LGG. It served as a poor prognostic marker in diffusely infiltrating gliomas. Based on its prognostic significance and strong correlation with CD163+ TAMs, it may act as an important therapeutic target for human glioma.

Project description:Osteosarcoma is the most common malignant bone tumor in adolescents and young adults, and identifying biomarkers for prognosis and therapy is necessary. Bone morphogenetic protein receptor 2 (BMPR2) is involved in various cellular functions, including cell adhesion, proliferation and invasion, inflammation, apoptosis and metastatic spread. However, the correlation between BMPR2 expression levels and prognosis and tumor-infiltrating immune cells in osteosarcoma is not well understood. In the present study, the expression level of BMPR2 was investigated using the Oncomine and R2 databases. The association between the expression level of BMPR2 and the clinical prognosis of patients with cancer was analyzed using the R2 database. The relationship between the expression level of BMPR2 and immune cell infiltration in the stroma of osteosarcoma was assessed using the Tumor Immune Estimation Resource (TIMER) and CIBERSORT. The correlations between BMPR2 expression level and infiltrated immune cell gene marker sets in osteosarcoma were validated in the TIMER and R2 databases. Analysis of a cohort of patients with osteosarcoma revealed that BMPR2 expression was significantly higher in osteosarcoma compared with in normal tissue and was correlated with poor prognosis. M0 macrophages, M2 macrophages, resting mast, γ δ T and CD8+ T cells were the top five immune cells with the highest degrees of infiltration in osteosarcoma. In addition, BMPR2 expression level showed a significant negative correlation with the gene markers of CD8+ T cells, monocytes and M2 macrophages. Low levels of infiltrating CD8+ T cells, monocytes or M2 macrophages in osteosarcoma was significantly associated with poor survival. These data suggested that CD8+ T cells, monocytes and M2 macrophages play significant roles in the establishment of the immune microenvironment of osteosarcoma. High BMPR2 expression was associated with poor prognosis and low infiltration of CD8+ T cells, monocytes and M2 macrophages in osteosarcoma. Hence, BMPR2 can be considered a biomarker of the immune infiltration, metastasis and prognosis of osteosarcoma.

Project description:BackgroundPIMREG is upregulated in multiple cancer types. However, the potential role of PIMREG in lung adenocarcinoma (LUAD) remains unclear. The present study aimed to explore its clinical significance in LUAD.MethodsUsing the Cancer Genome Atlas (TCGA) databases, we obtained 513 samples of LUAD and 59 normal samples from the Cancer Genome Atlas (TCGA) databases to analyze the relationship between PIMREG and LUAD. We used t and Chi-square tests to evaluate the level of expression of PIMREG and its clinical implication in LUAD. The prognostic value of PIMREG in LUAD was identified through the Kaplan-Meier method, Cox regression analysis, and nomogram. Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were performed to screen biological pathways and analyze the correlation of the immune infiltrating level with the expression of PIMREG in LUAD.ResultsPIMREG was highly expressed in patients with LUAD. Specifically, the level of PIMREG gradually increased from pathological stage I to IV. Further, we validated the higher expression of PIMREG expressed in LUAD cell lines. Moreover, PIMREG had a high diagnostic value, with an -AUC of 0.955. Kaplan-Meier survival and Cox regression analyses revealed that the high expression of PIMREG was independently associated with poor clinical outcomes. In our prognostic nomogram, the expression of PIMREG implied a significant prognostic value. Gene set enrichment analysis (GSEA) identified that the high expression PIMREG phenotype was involved in the mitotic cell cycle, mRNA splicing, DNA repair, Rho GTPase signaling, TP53 transcriptional regulation, and translation pathways. Next, we also explored the correlation of PIMREG and tumor-immune interactions and found a negative correlation between PIMREG and the immune infiltrating level of T cells, macrophages, B cells, dendritic cells (DCs) , and CD8+ T cells in LUAD.ConclusionsHigh levels of PIMREG correlated with poor prognosis and immune infiltrates in LUAD.

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Increased M1 Macrophages Infiltration Correlated With Poor Survival Outcomes and Radiation Response in Gliomas.

Publications

Increased M1 Macrophages Infiltration Correlated With Poor Survival Outcomes and Radiation Response in Gliomas.

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