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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Funding: This project was funded by Professor Stanley Sidhu of the Cancer Genetics 21 Laboratory at the Kolling Institute of Medical Research (NSLHD Cost Code CC 304618). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: 2020/ETH01931: Non-coding RNAs in Adrenocortical Cancer This project was considered by the Northern Sydney Local Health District Human Research Ethics Committee at a meeting of the Executive held on 12 August 2020 and was determined to meet the requirements of the National Statement on Ethical Conduct in Human Research (2007). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors