Prognostic value and immune cell infiltration of hypoxic phenotype‐related gene signatures in glioblastoma microenvironment

Xiao, Kai; Tan, Jun; Yuan, Jian; Peng, Gang; Long, Wenyong; Su, Jun; Xiao, Yao; Xiao, Qian; Wu, Changwu; Qin, Chaoying; Hu, Lili; Liu, Kaili; Liu, Shunlian; Zhou, Hao; Ning, Yichong; Ding, Xiaofeng; Liu, Qing

doi:10.1111/jcmm.15939

Cited by 16 publications

(17 citation statements)

References 36 publications

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“…In glioblastoma, extensive tissue hypoxia is commonly detected, and it can facilitate the formation of glioma stem-like cells, which is closely associated with tumor recurrence ( 7 ). Besides, hypoxia-related genes are demonstrated to correlate with the prognosis of glioma patients ( 8 , 9 ). Therefore, hypoxia is crucial for glioma development.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-Related lncRNA Correlates With Prognosis and Immune Microenvironment in Lower-Grade Glioma

Tang

Liu

et al. 2021

Front. Immunol.

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BackgroundHypoxia-related genes are demonstrated to correlate with the prognosis of various cancers. However, the role of hypoxia-related long non-coding RNAs (HRLs) in lower-grade glioma (LGG) remains unclear.MethodsA total of 700 LGG samples were extracted from TCGA and CGGA databases. Pearson correlation analysis was used to identify HRLs. Lasso analysis was adopted to construct the HRL signature. TIDE algorithm was used to predict responses to immune checkpoint inhibitors. Cell proliferation was estimated by cell counting kit-8 assay, colony formation assay, and EdU assay.ResultsWe identified 340 HRLs and constructed a novel risk signature composed of 19 HRLs. The risk score exhibited potent value in predicting the prognosis of LGG patients and was significantly associated with the prognosis of LGG patients. Moreover, HRL signature could distinguish patients with similar expression levels of immune checkpoints and might predict the efficacy of immune checkpoint inhibitors. Additionally, hypoxia-related pathways and immune pathways were enriched in high-risk group, and high risk score indicated low tumor purity and high immune infiltration. Two major HRLs, LINC00941 and BASP1-AS1, could significantly affect the proliferation of glioma cells.ConclusionsOur study constructed a novel HRL signature that could predict the prognosis and immunotherapy response of LGG patients. HRLs could be novel biomarkers to predict the prognosis of LGG patients and potential targets for LGG treatment.

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Section: Introductionmentioning

confidence: 99%

Hypoxia-Related lncRNA Correlates With Prognosis and Immune Microenvironment in Lower-Grade Glioma

Tang

Liu

et al. 2021

Front. Immunol.

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“…In recent years, the relationship between tumor immune microenvironment and immunotherapy has received more and more attention. It was also reported CHI3L1 was related to immune infiltration in breast cancer and glioblastoma (23,24). However, the data about the role of CHI3L2 in cancers and its association with immune infiltrates are fragmentary.…”

Section: Introductionmentioning

confidence: 99%

CHI3L2 Is a Novel Prognostic Biomarker and Correlated With Immune Infiltrates in Gliomas

et al. 2021

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CHI3L2 (Chitinase-3-Like Protein 2) is a member of chitinase-like proteins (CLPs), which belong to the glycoside hydrolase 18 family. Its homologous gene, CHI3L1, has been extensively studied in various tumors and has been shown to be related to immune infiltration in breast cancer and glioblastoma. High CHI3L2 expression was reported to be associated with poor prognosis in breast cancer and renal cell carcinoma. However, the prognostic significance of CHI3L2 in glioma and its correlation between immune infiltration remains unclear. In this study, we examined 288 glioma samples by immunohistochemistry to find that CHI3L2 is expressed in tumor cells and macrophages in glioma tissues and highly expressed in glioblastoma and IDH wild-type gliomas. Relationships between CHI3L2 expression and clinical features (grade, age, Ki67 index, P53, PHH3 (mitotic figures), ATRX, TERTp, MGMTp, IDH, and 1p/19q co-deleted status) were evaluated. Kaplan-Meier survival was conducted to show high CHI3L2 expression in tumor cells (TC) and macrophage cells (MC) indicated poor prognosis in diffusely infiltrating glioma (DIG), lower-grade glioma (LGG), and IDH wild-type gliomas (IDH-wt). The overall survival time was higher in patients with dual-low CHI3L2 expression in TC and MC compared to those in patients with non-dual CHI3L2 expression and dual high expression in DIG and IDH wild-type gliomas. By univariate and multivariate analysis, we found that high CHI3L2 expression in tumor cells was an independent unfavorable prognostic factor in glioma patients. Moreover, we used two datasets (TCGA and CGGA) to verify the results of our study and explore the potential functional role of CHI3L2 by GO and KEGG analyses in gliomas. TIMER platform analysis indicated CHI3L2 expression was closely related to diverse marker genes of tumor immune infiltrating cells, including monocytes, TAMs, M1 macrophages, M2 macrophages, TGFβ1+ Treg and T cell exhaustion in GBM and LGG. Western Blot validated CHI3L2 is expressed in glioma cells and microglia cells. The results of flow cytometry showed that CHI3L2 induces the apoptosis of CD8+ T cells. In conclusion, these results demonstrate CHI3L2 is related to poor prognosis and immune infiltrates in gliomas, suggesting it may serve as a promising prognostic biomarker and represent a new target for glioma patients.

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“…Moreover, Xiao et al established a four-gene tumor microenvironment-related model based on TCGA-GBM dataset. These four genes were reported to potentially be associated with the hypoxic phenotype of glioblastoma [21]. Furthermore, Gong et al divided the breast cancer patients from TCGA database into two groups based on the expression of 13 hypoxia-related genes.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of The Significance of Hypoxia-Related Genes in Ovarian Cancer

Zhao

Yin

2021

Preprint

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Background: Hypoxia-related genes have been reported to play important roles in a variety of cancers. However, their roles in ovarian cancer (OC) have remained unknown. Our aim was to explore the significance of hypoxia-related genes in OC patients.Methods: In this study, 15 hypoxia-related genes were screened from The Cancer Genome Atlas (TCGA) database to group the ovarian cancer patients using the consensus clustering method. Principal component analysis (PCA) was used to calculate the hypoxia score to quantify the hypoxic status. Results: The OC patients were divided into two hypoxia statuses based on the expression level of the 15 hypoxia-related genes. Most hypoxia-related genes were more highly expressed in the cluster.A group. We also found that patients in the cluster.A group exhibited higher expression level of immune checkpoint-related genes, epithelial-mesenchymal transition-related genes, and immune activation-related genes, as well as elevated immune infiltrates. PCA algorithm indicated that the cluster.A group had higher hypoxia scores.Conclusions: In summary, our research elucidated the vital role of hypoxia-related genes in immune infiltrates of OC. Our investigation of hypoxic status may be able to improve the efficacy of immunotherapy for OC.

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Prognostic value and immune cell infiltration of hypoxic phenotype‐related gene signatures in glioblastoma microenvironment

Cited by 16 publications

References 36 publications

Hypoxia-Related lncRNA Correlates With Prognosis and Immune Microenvironment in Lower-Grade Glioma

Hypoxia-Related lncRNA Correlates With Prognosis and Immune Microenvironment in Lower-Grade Glioma

CHI3L2 Is a Novel Prognostic Biomarker and Correlated With Immune Infiltrates in Gliomas

Comprehensive Analysis of The Significance of Hypoxia-Related Genes in Ovarian Cancer

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