Comparative Proteomic Profiling of Adrenocortical Neoplasia Using Mass Spectrometry.

Recent advances in high-throughput molecular analysis have significantly enhanced our understanding of the molecular mechanisms underlying adrenocortical diseases. To identify differences in protein signatures that may reveal insights into disease-specific pathogenesis, we used LC-MS/MS and bioinformatics to compare proteomic profiles of normal human adrenal (NHA) tissue, adrenocortical adenomas (ACA), adrenocortical carcinomas (ACC), and primary macronodular adrenocortical hyperplasia (PMAH) tumors, with and without ARMC5 mutations. In total, 7350 proteins were identified, and 3976 were quantified across all samples. Differentially expressed proteins (DEPs) were found in ACA vs NHA (27 DEPs), ACC vs NHA (49 DEPs), and PMAH vs NHA (81 DEPs). Comparing ACC and ACA revealed 64 upregulated and 48 downregulated DEPs. PMAH with ARMC5 mutations (PMAHw) vs without ARMC5 mutations (PMAHwt) had the fewest DEPs, 12 upregulated and 4 downregulated proteins in PMAHw. These findings were validated using an independent ACC cohort from Seoul National University Hospital, which showed 99.8% overall similarity and with no significant disparities. This comprehensive profiling of NHA, ACA, ACC, and PMAH offers insights into normal adrenal function and tumor-associated changes. Our study presents a high-quality proteomic data set, highlighting potential biomarkers and therapeutic targets, and makes a significant contribution to the understanding of adrenocortical disease mechanisms.