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.