Integrated single-cell and transcriptome sequencing data reveal the value of AOC1 in gliomas tumor microenvironment and prognosis

Glioma is a primary brain tumor that is frequently encountered in humans, with malignant gliomas representing an exceptionally aggressive subtype. The role of AOC1 in the progression of various human tumors has been documented; however, its involvement in gliomas (including distinct WHO grades, namely WHO Grade IV glioblastoma multiforme [GBM] and WHO Grades II–III low-grade gliomas [LGG]), remains largely unexplored. We analyzed RNA sequencing data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases to assess AOC1 expression. We performed transcriptomic analysis and differential gene expression studies based on AOC1 levels in TCGA sequencing data. Functional analyses exploring the signaling pathways involved in AOC1. CIBERSORT, single-sample Gene Set Enrichment Analysis (ssGSEA), and ESTIMATE were employed to estimate the tumor microenvironment in gliomas. Analyzing the single-cell sequencing data further revealed the value of AOC1 played in intercellular communication. Finally, the mechanism of AOC1 involvement in gliomas was verified by cellular and molecular experiments. High tumor expression of AOC1 is associated with lower patient survival. Our analyses revealed that cytokine signaling pathways are significantly suppressed in AOC1-high GBMLGG tissues. Q-PCR results corroborated that AOC1 inhibits IL17, IL6 and IL1β secretion in GBM cells. The CIBERSORT analysis showed a significant increase in the proportion of M2 macrophages in AOC1-high cancer tissues. Cell-cell communication analysis indicated that the MIF signaling network between AOC1-high GBMLGG tumor cells and macrophages is notably weakened. Additionally, AOC1 silencing directly delays the proliferation and migration of GBMLGG cells in vitro. Tumor AOC1 levels can serve as a molecular marker for diagnosis and molecular subtyping. As a secreted protein, AOC1 holds promise as a new target for non-invasive molecular diagnosis and precision therapy in GBMLGG.