Endocrine Abstracts

Neuroendocrine neoplasms (NENs) are a highly heterogeneous group of tumors that arise from the diffuse neuroendocrine system and whose incidence has increased over the last years. Among them, pancreatic NENs (PanNENs) are relatively common and one of the most studied NENs. PanNENs are characterized by a low number of mutations, with some genes frequently mutated, such as MEN1, ATRX/DAXX, and mTOR signaling pathway genes. Despite genomics, transcripto...

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a growing cause of hepatocellular carcinoma (HCCs); however, the molecular characteristics of MAFLD-derived HCCs are still to be elucidated. To provide novel insights in this field, we performed the first quantitative proteomic analysis of HCC samples from different aetiologies. Particularly, cytosolic and nuclear proteome of liver tissues from HCC patients (n=42; HCC vs adjacent tissue) and healthy contr...

Background: Molecular classification is important for diagnosis and prognosis of adrenocortical tumors (ACT). Transcriptome profiles separate benign ACT (“C2” cluster) from carcinomas (ACC) and identify two groups of ACC, “C1A” (“steroid” and “proliferation” signatures) and “C1B” (“immune” signature), of poor and better prognosis respectively. However, these signatures were characterized at the tissue level (“bul...

Background: Adrenocortical carcinoma (ACC) is a very rare and aggressive, endocrine malignancy with still limited treatment options. Approximately 60% of patients with ACC show endogenous glucocorticoid excess which could be one potential cause, why first clinical trials with immunotherapies, like immune checkpoint inhibitors, showed only modest results. Due to the lack of an ACC-specific antigen structure, other immunotherapeutic approaches, like specialized cancer treatments...

Background: Adrenocortical cancer (ACC) is a rare malignant neoplasm with a dismal prognosis, particularly in advanced disease. For these patients only limited therapeutic options are available. Adavosertib (AZD1775) is a potent inhibitor of tyrosine kinase WEE1 that regulates cell cycle checkpoints, slowing cell cycle progression and leading to mitotic entry in the presence of DNA damage. Therefore, its use could potentiate existing DNA damage-based therapies. Here, we evalua...

Background: Molecular mechanisms of malignant adrenocortical tumorigenesis remain elusive despite previous comprehensive genomic studies. Nonetheless, cellular heterogeneity of primary, recurrent and metastatic adrenocortical carcinoma (ACC) haven’t been fully investigated.Aim: To characterize the molecular profile of different cell subtypes in primary, recurrent and metastatic ACC by single-nuclei RNA sequencing (snRNA-Seq), using adult human norma...