7362 Single-Cell Analysis Of Cortisol-Producing Adrenal Adenomas

Abstract Disclosure: T. Kono: None. M. Fujimoto: None. Y. Taki: None. T. Tanaka: None. Introduction: Cortisol-producing adenoma (CPA) is a common adrenal tumor. Although the contribution of mutations to the pathogenesis of CPA is well-established, mutations alone cannot explain all the diverse clinical manifestations. Therefore, it is important to observe the nature of the tumor from a different perspective, based on the clinical features, and understand the pathogenesis of the disease. Recently, single-cell analysis techniques have been developed to accurately define and analyze diverse cell populations, such as tumor cells, immune cells, and stromal cells, in tumor tissues. It is expected that these techniques will reveal the nature of tumor cells that were not visible in the averaged analysis of the entire tumor. Method: We performed genetic mutation analysis and single-cell RNA sequencing on 58 samples of normal adrenal tissue and 13 cases of CPA. Result: The results showed that both normal adrenal tissue and CPA tumor tissue were composed of various cells, including adrenal cortical cells, immune cells dominated by macrophages and T cells, endothelial cells, and fibroblasts. The genetic mutations of CPA are mainly divided into two groups: (1) mutations in PRKACA and GNAS that contribute to the activation of the cAMP pathway and (2) mutations in CTNNB1 that contribute to the activation of the Wnt pathway. Based on the patterns of genetic mutations, we divided the tumor cells into four groups: PRKACA, GNAS, CTNNB1, and N.D. (Not detected). We then used single-cell analysis of tumor cells to observe the differences in their nature using consensus clustering and module analysis. The results showed that the cluster with the most cells with PRKACA mutations was the largest, and the steroidogenesis gene cluster showed correlated changes. Conclusion: Single-cell analysis revealed that the adrenal tissue is composed of diverse cell populations, and it was possible to identify and analyze specific cell populations. In the future, it is necessary to clarify the relationship between tumor cell origin and zonation, as well as to develop new disease phenotypes and classifications based on the interactions between diverse cells that construct the tissue. Presentation: 6/1/2024