Project description:The molecular pathogenesis of adrenocortical diseases, particularly adrenocortical carcinoma (ACC), has advanced considerably in recent years due to the application of high-throughput molecular analysis. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) offers an approach for identifying and quantifying numerous proteins in biological samples. Aiming to identify differences in adrenal cortex disease protein signatures that may contribute to understanding their distinct pathogenesis, we used LC-MS/MS and bioinformatics analysis to compare the proteomic profiles of normal human adrenal samples (NHA), adrenocortical adenomas (ACA), adrenocortical carcinomas (ACC), and primary macronodular adrenocortical hyperplasia (PMAH) tumor samples, with (w) and without (wt) ARMC5 mutation. A total of 7,350 proteins were identified, with 3,976 proteins quantified in all analyzed samples, and differentially expressed proteins (DEPs) noted as upregulated and downregulated were highlighted as relevant. We identified 27 DEPs in ACA vs. NHA, where MT3 and RBM3 are upregulated, and NEFL, HAAO, SOD3, IGHA2, and HDGFL3 are the top five of 25 downregulated proteins; 49 DEPs in ACC vs. NHA, with DEFA3, NUP160, SRRM2, and RBM3 upregulated, alongside SOD3, CNRIP, DNAH1, GAMT, ADIRF, and CA3 as the top six of 45 downregulated proteins; 81 DEPs in PMAH vs. NHA, with RBM3, RIGI, SPAG9, and SRRM2 proteins as the top four of 9 upregulated proteins, and 72 downregulated proteins with AFM, CA 3, IGKV1-5, ADIRF, and LRG1 as the top five; ACC vs. ACA identified 64 upregulated and 48 downregulated DEPs, with PHGDH (SERA), PDCD4, MAGED2, ERAP2, FTO, DUSP23, UBLCP 1, NSUN2, TP53BP1, NUP107 as the top ten upregulated, and RMDN2, CSRP1, ACAD11, PACSIN3, HAGH (GLO2), ALG5, NEXN, ABLIM1, LBP, and SYNPO2 as the top ten downregulated in ACC. DEPs analysis in PMAHw vs. PMAHwt showed the lowest number of DEPs, with NOSTRIN, PCP4, C4 BPB, and SERB (PSPH) as the top four of 12 upregulated proteins, and 4 downregulated proteins EST2 (TERT), PNPT1, RDH13, and STAB1 in PMAHw. Comparative analysis highlighted several targets for functional analysis and validation to determine the mechanism of action and protein biomarkers.
2025-12-15 | PXD062822 | Pride
Junxia Yang 
