Unravelling the Tumourigenesis Mechanisms of Oncocytic Cell Tumours: Discoveries from a Comparative Omics Study

Abstract

Oncocytic cell tumours (OCTs), formerly known as Hürthle cell tumours in thyroid, are a subset of thyroid and other endocrine neoplasms that present diagnostic and therapeutic challenges due to their variable clinical behaviour. Considering the limited exploration of transcriptomic and proteomic profiles of OCTs compared to MRNs in the literature, we conducted RNA and protein sequencing on 12 OCTs (5 oncocytic adenomas and 7 oncocytic carcinomas) and 6 MRNs, based on the fact that oncocytic morphology alone does not determine biological behavior. RNA sequencing data analysis revealed the presence of 47 downregulated and 38 upregulated differentially expressed genes (DEGs) in OCTs when compared to MRNs. Significant signalling pathways affecting OCTs were associated with the heme metabolism. Protein sequencing data analysis showed the presence of 20 underexpressed and 64 overexpressed differentially expressed proteins (DEPs) in OCTs than in MRNs, and all of the OCAs were found to cluster together, constituting a distinct cluster than the one comprising the MRNs. The majority of DEPs affected three major cellular pathways in OCTs, including epigenetic modifications, tumor microenvironment, and protein biogenesis, that may shape the behavior and morphology of these tumors. Hence, further research into these mechanisms and their impact on tumour phenotype and behaviour may lead to better diagnostic and therapeutic strategies for patients with OCTs.