Denticleless E3 Ubiquitin Protein Ligase Homolog as a Potential Biomarker for Adrenocortical Carcinoma Screening

Objective: This study aims to investigate the potential of denticleless E3 ubiquitin protein ligase homolog (DTL) as a biomarker for adrenocortical carcinoma (ACC) detection through bioinformatics analysis and experimental validation. Methods: Differentially expressed genes (DEGs) between ACC and adrenocortical adenoma (ACA) were identified through bioinformatics analysis. A protein-protein interaction (PPI) network was constructed using Cytoscape software, and core genes were screened with the CytoHubba MCODE plug-in. Survival analysis was performed using the University of ALabama at Birmingham CANcer (UALCAN) data analysis portal. Immunohistochemistry was employed to assess DTL expression in adjacent normal tissues, ACA, and ACC. Results: Two gene expression series (GSEs) retrieved from the Gene Expression Omnibus (GEO) database yielded 115 DEGs. Using the PPI network, three core genes were identified, among which DTL and TPX2 were highly expressed in ACC. Notably, DTL had the highest core gene score. Elevated DTL expression in individuals with ACC was significantly associated with a poor prognosis (P < 0.0001). Immunohistochemistry analysis revealed a significantly higher positive expression rate and a strong positive expression rate of DTL in ACC compared to ACA (χ2 = 11.708, P < 0.01). The positive expression rate of DTL in both ACC and ACA was significantly higher than in the adjacent normal adrenal cortex (P < 0.01). The expression of DTL followed a gradient, being highest in ACC, followed by ACA, and lowest in the normal adrenal cortex adjacent to the tumor. Additionally, DTL protein expression was significantly correlated with tumor size and infiltration metastasis (P < 0.05). Individuals with high DTL expression had significantly shorter survival times than those with low DTL expression (P < 0.05). Conclusion: DTL exhibits potential as a novel biomarker for distinguishing between benign and malignant adrenocortical tumors and may serve as a prognostic indicator for ACC.