GULP1 in Ovarian Cancer: Expression, Biological Function, and Clinical Significance

As an engulfment adapter for apoptotic clearance, GULP1 is related to tumor progression, but its role in ovarian cancer (OVCA) remains unclear.

GULP1 expression, copy number variations (CNVs), and their correlations were analyzed using datasets collected from The Cancer Genome Atlas (TCGA)-OVCA and the Gene Expression Profiling Interactive Analysis (GEPIA). Gene set enrichment analysis (GSEA), immune infiltration assessment, and drug sensitivity prediction were conducted to identify pathways enriched by GULP1 and to explore its potential association with drug sensitivity. The binding affinity of candidate drugs to GULP1 was evaluated through molecular docking. Finally, cellular assays were performed to explore the biological functions of GULP1 in OVCA cells.

GULP1 was downregulated in OVCA, particularly in advanced stages. The GULP1 expression was associated with enrichment of hypoxia, EMT, angiogenesis, and TGFβ signaling, which were correlated with immune evasion. LFM-A13 demonstrated binding affinity for GULP1 (ΔG = -5.85 kcal/mol). Overexpression of GULP1 inhibited migration and invasion of A2780 and SK-OV-3 cells. Conversely, GULP1 knockdown exerted the opposite effects.

This study explored the role of GULP1 in OVCA and analyzed its correlation with the immune microenvironment and key pathways. Molecular docking predicted LFM-A13 as a potential therapeutic agent for OVCA; however, its efficacy remains to be clinically verified.

The current findings reveal GULP1 as a novel biomarker for OVCA progression and immune escape, highlighting its role in modulating the tumor microenvironment (TME). Targeting GULP1 with LFM-A13 may offer a potential strategy for OVCA precision therapy.