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

Xin Yan; Li-Xing Pang; Xiao Lu; Sheng Chen; Li Li; Xing-Huan Liang; De-Cheng Lu; Zuo-Jie Luo

doi:10.2174/0118715303334496250518033852

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

Endocr Metab Immune Disord Drug Targets. 2025 Jun 20. doi: 10.2174/0118715303334496250518033852. Online ahead of print.

Authors

Xin Yan^{1

2}, Li-Xing Pang¹, Xiao Lu¹, Sheng Chen¹, Li Li², Xing-Huan Liang², De-Cheng Lu², Zuo-Jie Luo²

Affiliations

¹ Department of Endocrinology, The Second People's Hospital of Nanning City, The Third Affiliated Hospital of Guangxi Medical University, Nanning 530031, Guangxi Province, China.
² Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Province, China.

PMID: 40574400
DOI: 10.2174/0118715303334496250518033852

Abstract

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.

Keywords: (DTL).; Adrenocortical carcinoma; bioinformatics; biomarkers.