ANXA1 as a Prognostic and Immune Microenvironmental Marker for Gliomas Based on Transcriptomic Analysis and Experimental Validation

Lin, Zhongxiao; Wen, Ming‐Shien; Yu, Enxing; Lin, Xiao Yan; Wang, Hua; Chen, Jiayu; Yao, Chaojie; Zhang, Hengli; Ru, Junnan; Wang, Kankai; Zhang, Ying; Huang, Lijie; Zhuge, Qichuan; Yang, Shuxu

doi:10.3389/fcell.2021.659080

Cited by 10 publications

(13 citation statements)

References 48 publications

(48 reference statements)

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“…To explore the exhaustive function of ANXA1 in gliomas, we integrated the bulk genomic and transcriptomic profiles and scRNA-seq data to comprehensively characterize the role of ANXA1 in gliomas. In this study, we revealed that ANXA1 was significantly upregulated in GBM patients, especially enriched in IDH wild-type gliomas, which was consistent with previous reports ( Lin et al, 2021 ; Qiu et al, 2020 ). In addition, gliomas with chemotherapy and/or radiotherapy tend to have a high ANXA1 expression.…”

Section: Discussionsupporting

confidence: 93%

“…Previous studies suggest that loss of function or expression of this gene has been implicated in multiple functions essential in cancer, including cell proliferation, apoptosis, chemosensitivity, metastasis, and invasion ( Bai et al, 2020 ; Feng et al, 2020 ; Xiong et al, 2021 ). Recently, Lin et al investigated the prognostic and immune role of ANXA1 in gliomas ( Lin et al, 2021 ). However, the systematic and comprehensive transcriptome characterization of ANXA1 in gliomas is unclear.…”

Section: Introductionmentioning

confidence: 99%

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Molecular Characterization and Clinical Relevance of ANXA1 in Gliomas via 1,018 Chinese Cohort Patients

Qian

Fan

Meng

et al. 2021

Front. Cell Dev. Biol.

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Annexin A1 (ANXA1) is a calcium-dependent phospholipid-binding protein and has been implicated in multiple functions essential in cancer, including cell proliferation, apoptosis, chemosensitivity, metastasis, and invasion. However, the biological role and clinical behavior of ANXA1 in glioma remain unclear. In this study, RNA-seq (n = 1018 cases) and whole-exome sequencing (WES) (n = 286 cases) data on a Chinese cohort, RNA-seq data with different histological regions of glioblastoma blocks (n = 270 cases), and scRNA-seq data (n = 7630 cells) were used. We used the R software to perform statistical calculations and graph rendering. We found that ANXA1 is closely related to the malignant progression in gliomas. Meanwhile, ANXA1 is significantly associated with clinical behavior. Furthermore, the mutational profile revealed that glioma subtypes classified by ANXA1 expression showed distinct genetic features. Functional analyses suggest that ANXA1 correlates with the immune-related function and cancer hallmark. At a single-cell level, we found that ANXA1 is highly expressed in M2 macrophages and tumor cells of the mesenchymal subtype. Importantly, our result suggested that ANXA1 expression is significant with the patient’s survival outcome. Our study revealed that ANXA1 was closely related to immune response. ANXA1 plays a key factor in M2 macrophages and MES tumor cells. Patients with lower ANXA1 expression levels tended to experience improved survival. ANXA1 may become a valuable factor for the diagnosis and treatment of gliomas in clinical practice.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Molecular Characterization and Clinical Relevance of ANXA1 in Gliomas via 1,018 Chinese Cohort Patients

Qian

Fan

Meng

et al. 2021

Front. Cell Dev. Biol.

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“…Recent studies proven that targeting ANXA1 abrogated Treg-mediated immune suppression in triple-negative breast cancer and ANXA1 was considered as a worse prognostic and TME marker in gliomas. (24, 25) FASN is abnormally expressed in lots of tumors and is highly related to tumor migration and invasion (26). FNDC4 promotes the tumor invasiveness of hepatocellular cancer as an extracellular factor to (27).…”

Section: Discussionmentioning

confidence: 99%

Analysis and Identification of Necroptosis Landscape on Therapy and Prognosis in Bladder Cancer

Zhao

Jiang

Zhang

et al. 2022

Preprint

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Bladder cancer (BLCA) is one of the most common malignant tumors of the urinary system, but current therapeutic strategy based on chemotherapy and immune checkpoint inhibitors (ICIs) therapy cannot meet the treatment needs, which mainly owing to the endogenous or acquired apoptotic resistance of cancer cells. Targeting necroptosis provides a novel strategy for chemotherapy, targeted drugs, and improves the efficacy of ICIs because of strong immunogenicity of necroptosis. Therefore, we systemically analyzed necroptosis landscape on therapy and prognosis in BLCA. We firstly divided BLCA patients from The Cancer Genome Atlas (TCGA) database into two necroptosis-related clusters (C1 and C2). Necroptosis C2 showed a significantly better prognosis than C1, and the differential genes of C2 and C1 were mainly related to the immune response according to GO and KEGG analysis. Next, we constructed a novel necroptosis related genes (NRGs) signature consisting of SIRT6, FASN, GNLY, FNDC4, SRC, ANXA1, AIM2, and IKBKB to predict the survival of TCGA-BLCA cohort, the accuracy of NRGsocre was also verified by external datasets. In addition, a nomogram combining NRGscore and several clinicopathological features was established to predict the BLCA patient’s OS more accurately and conveniently. We also found that NRGscore was significantly related to the infiltration levels of CD8 T cells, NK cells, and iDC cells, the gene expression of CTLA4, PD1, TIGIT, and LAG3 of TME, the sensitivity to chemotherapy and targeted agents in BLCA patients. In conclusion, the NRGscore has an excellent performance in evaluating the prognosis, clinicopathologic features, tumor microenvironment (TME) and therapeutic sensitivity of BLCA patients, which could be utilized as a guide for chemotherapy, ICIs therapy, and combination therapy.

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“…Also, our results corroborated these analyses. ANXA1 had just been reported as a prognostic and immune microenvironmental marker in glioma ( Lin et al, 2021 ; Qian et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the IDH1 mutant had been widely recognized as one of the indicators for molecular typing of glioma ( Pirozzi and Yan, 2021 ). Also, ANAX1 , another NRG, might act as a regulator of cell-mediated immunity in low-grade glioma (LGG) TME by activating T cells ( Lin et al, 2021 ). Celastrol derivatives were verified as novel potential selections in glioma therapy due to their functions in necroptosis ( Feng et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

A novel necroptosis-related gene signature for predict prognosis of glioma based on single-cell and bulk RNA sequencing

Guo

Duan

Zhao

et al. 2022

Front. Mol. Biosci.

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Background: Glioma is the most fatal neoplasm among the primary intracranial cancers. Necroptosis, a form of programmed cell death, is correlated with tumor progression and immune response. But, the role of necroptosis-related genes (NRGs) in glioma has not been well-uncovered.Methods: Single-cell and bulk RNA sequencing data, obtained from publicly accessed databases, were used to establish a necroptosis-related gene signature for predicting the prognosis of glioma patients. Multiple bioinformatics algorithms were conducted to evaluate the efficacy of the signature. The relative mRNA level of each signature gene was validated by quantitative real-time reverse transcription PCR (qRT-PCR) in glioma cell lines compared to human astrocytes.Results: In this predicted prognosis model, patients with a high risk score showed a shorter overall survival, which was verified in the testing cohorts. The signature risk score was positively related with immune cell infiltration and some immune check points, such as CD276 (B7-H3), CD152 (CTLA-4), CD223 (LAG-3), and CD274 (PD-L1). Single-cell RNA sequencing analysis confirmed that the glioma microenvironment consists of various immune cells with different markers. The eight NRGs of the signature were detected to be expressed in several immune cells. QRT-PCR results verified that all the eight signature genes were differentially expressed between human astrocytes and glioma cells.Conclusion: The eight NRGs correlate with the immune microenvironment of glioma according to our bioinformatics analysis. This necroptosis-related gene signature may evaluate the precise methodology of predicting prognosis of glioma and provide a novel thought in glioma investigation.

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ANXA1 as a Prognostic and Immune Microenvironmental Marker for Gliomas Based on Transcriptomic Analysis and Experimental Validation

Cited by 10 publications

References 48 publications

Molecular Characterization and Clinical Relevance of ANXA1 in Gliomas via 1,018 Chinese Cohort Patients

Molecular Characterization and Clinical Relevance of ANXA1 in Gliomas via 1,018 Chinese Cohort Patients

Analysis and Identification of Necroptosis Landscape on Therapy and Prognosis in Bladder Cancer

A novel necroptosis-related gene signature for predict prognosis of glioma based on single-cell and bulk RNA sequencing

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