Abstract
OBJECTIVE: This research seeks to comprehensively explore the expression patterns of Angiopoietin-2 (ANGPT2) in pan-cancer and examine its relationship with clinical outcomes, tumor immune microenvironment dynamics, and biological functions, with particular emphasis on skin cutaneous melanoma (SKCM). METHODS: Data from six databases, including UCSC Xena, TCGA, GTEx, TIMER2.0, GEPIA, and cBioPortal, were analyzed to assess ANGPT2 expression in pan-cancer. Immunohistochemical images were sourced from the HPA database. We explored the correlation between ANGPT2 expression and prognosis, diagnostic value, genetic alterations, and immune cell infiltration in cancers. Functional enrichment and gene set enrichment analyses were performed to uncover the biological roles of ANGPT2. Additionally, miRWalk, miRDB, Starbase 2.0 ENCORI, and Cytoscape were utilized to identify and construct the lncRNA-miRNA-ANGPT2 ceRNA regulatory network in SKCM. RESULTS: Our comprehensive pan-cancer analysis revealed that ANGPT2 undergoes genetic alterations in several tumor types, including mutations, amplifications, and deep deletions. ANGPT2 expression varies across cancers, with high levels detected in 21 tumor types. ANGPT2 demonstrated significant diagnostic and prognostic value in various cancers. Genes related to ANGPT2 in cancers with high expression were found to be involved in critical pathways such as tumor angiogenesis, growth factor signaling, extracellular matrix (ECM) structure, and cell surface receptor activation. In addition, ANGPT2 was found to modulate the immune microenvironment in multiple tumors, promoting immune evasion and contributing to tumor progression, particularly in SKCM. A lncRNA-miRNA-ANGPT2 ceRNA regulatory network was identified, which may play a role in SKCM progression. CONCLUSIONS: ANGPT2 demonstrates potential as a biomarker for cancer diagnosis and prognosis, with evidence suggesting its involvement in immune microenvironment regulation and associated gene networks. Therapeutic approaches targeting ANGPT2, either as a stand-alone treatment or in combination with immunotherapies, could offer new and effective strategies for future cancer treatments.