Abstract
OBJECTIVES: Actin filament-associated protein 1 like 1 (AFAP1L1) is an adaptor protein lacking enzymatic and transcriptional activity, but the AFAP1L1 gene functions as an oncogene in colorectal cancer and gastric cancers. This study aims to investigate the role of AFAP1L1 in glioma and to explore changes in AFAP1L1 expression during glioma progression. METHODS: Clinical and transcriptomic data of glioma patients were downloaded from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), and the Gene Expression Omnibus (GEO) databases to analyze the associations between AFAP1L1 expression and glioma prognosis, somatic mutations, immune cell infiltration, and enriched signaling pathways. Western blotting and real-time polymerase chain reaction (PCR) were used to detect AFAP1L1 messenger RNA (mRNA) and protein expression in glioma patients. RESULTS: Patients with high AFAP1L1 expression had poorer prognosis, and AFAP1L1 was identified as an independent risk factor for glioma. In addition, glioma patients with high AFAP1L1 expression exhibited lower levels of somatic mutations, including amplification of oncogenes such as epidermal growth factor receptor and deletion of tumor suppressor genes such as cyclin-dependent kinase inhibitor 2A (CDKN2A). Estimation of STromal and Immune cells in Malignant Tumours using Expression (ESTIMATE) algorithm analysis showed that AFAP1L1 expression was positively correlated with the immune microenvironment. Tumor immune dysfunction and exclusion (TIDE) analysis indicated that glioma patients with high AFAP1L1 expression responded poorly to immunotherapy. Single cell analysis showed that AFAP1L1 expression was mainly concentrated in glioma cells. Enrichment analysis suggested that AFAP1L1 was potentially associated with small guanosine triphosphatases (GTPases), hypoxia-inducible factor-1 (HIF-1), focal adhesion, and mitogen-activated protein kinase (MAPK) signaling pathways. CONCLUSIONS: AFAP1L1 is a novel biomarker indicating glioma progression and a potential therapeutic target for glioma.