ANGPT1 as a Key Regulator in Tumor Microenvironment and Immunotherapy Response Across Multiple Cancers: A Pan-cancer Analysis

Angiopoietin 1 (ANGPT1) is a key regulator in the tumor microenvironment (TME), influencing tumor progression, immune modulation, and therapy response. However, a systematic pan-cancer analysis of ANGPT1’s role is lacking. In this study, we performed a comprehensive bioinformatics analysis using datasets from multiple databases to explore ANGPT1’s prognostic significance, its interaction with immune cells in the TME, and its potential as a therapeutic target across various cancers. We examined ANGPT1’s association with tumor prognosis, mutation load, microsatellite instability, immune cell infiltration, immune checkpoint genes, and drug sensitivity. Additionally, we analyzed ANGPT1 expression in acute myeloid leukemia (AML) patients, comparing complete remission (CR) versus no response (NR) groups, and investigated its effect on AML cell proliferation through loss-of-function assays. Our results showed significant heterogeneity in ANGPT1 mRNA expression across 10 of 33 cancer types, with high expression in glioblastoma multiforme and kidney chromophobe, and lower expression in other tumors. High ANGPT1 immunohistochemical scores were significantly associated with poor prognosis in six cancers. Furthermore, ANGPT1 expression correlated with immune-related markers, tumor mutational burden, microsatellite instability, and immune regulation. Drug sensitivity predictions revealed that ANGPT1 expression influenced tumor sensitivity to various drugs. Importantly, ANGPT1 was significantly upregulated in AML patients, with higher levels in the NR group compared to the CR group, and it promoted AML cell proliferation. These findings highlight ANGPT1 as a pivotal regulator in the TME, influencing immune responses and drug sensitivity, making it a potential prognostic biomarker and therapeutic target in cancer immunotherapy.