AGO2 protein: A Key Enzyme in the miRNA Pathway as a Diagnostic and Prognostic Biomarker in Adrenocortical Carcinoma

Context Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy. Current treatment algorithms are associated with diagnostic limitations, high recurrence rates and poor prognosis. Identifying specific biomarkers that facilitate accurate diagnosis and provide prognostic insights could significantly enhance the patient outcomes in ACC. Objective To investigate whether microRNA machinery, specifically argonaute 2 (AGO2), a key enzyme in the miRNA pathway, has the potential to be a diagnostic and prognostic biomarker for adrenocortical carcinoma (ACC). Design This study analyzed mRNA expression of genes involved in the miRNA biogenesis pathway using RNASeq data from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) dataset, followed by target protein quantification in tissue samples using commercial ELISA kits. Setting Publicly available mRNASeq datasets (TCGA-GTEX) and frozen tissue samples from the tumour bank of the Kolling Institute of Medical Research. Participants We analyzed data for 79 ACC and 190 normal adrenal cortex (NAC) samples from the TCGA and GTEx datasets, as well as for 31 other cancer types from the TCGA. We then performed protein quantification in 15 NAC, 15 benign adrenal adenoma (AA), and 15 ACC tissue homogenates. Intervention(s) None. Main Outcome Measures AGO2 mRNA and protein expression in ACC and its prognostic correlation. Results AGO2 was significantly overexpressed in ACC, compared to NAC and AA (p<0.001). Kaplan– Meier survival analysis revealed that higher expression of AGO2 was associated with significantly worse overall survival in ACC (HR 7.07, p<0.001). Among all 32 cancer types in TCGA, AGO2’s prognostic utility was most significant in ACC. Conclusions AGO2 holds potential as a diagnostic and distinct prognostic biomarker in ACC.