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

Abstract

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.

In-depth quantitative proteomics analysis revealed C1GALT1 depletion in ECC-1 cells mimics an aggressive endometrial cancer phenotype observed in cancer patients with low C1GALT1 expression

“…nine were selected for validation. In addition, in vitro lossof-function assays using shC1GALT1 and SCRAMBLE ECC-1 cells confirmed the more tumorigenic and aggressive phenotype of ECC-1 cells due to C1GALT1 depletion, bladder, endometrial, colorectal, lung and pancreatic cancer, and melanoma [70][71][72][73][74]. Previous works described ANXA1 upregulated in the secretome and exosomes secreted by cancer cells [75], which has been associated with a major potential role of ANXA1 in promoting cancer angiogenesis, proliferation, invasion and metastatic properties of cancer cells [43,44].…”

Clinical Characterization and Prognostic Value of TPM4 and Its Correlation with Epithelial–Mesenchymal Transition in Glioma

“…In tumor cells and macrophages, TPM4 expression showed an increasing trend as the WHO grade increased, suggesting that TPM4 abnormality was mainly attributed to tumor progression and tumor-associated macrophage (TAM) infiltration, which was further confirmed in the subsequent pseudotime trajectory analysis. As a critical cell subpopulation of TME, TAMs have been concluded to play a vital role in promoting the genesis and progression of glioma [ 31 , 32 ]. Particularly, M2 polarization of macrophages is significantly associated with aggressive progression across different malignancies, especially with immune escape of tumor cells.…”

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

“…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 ).…”