Molecular Characterization of Human ACTH-producing Tumors

The aim of this study is the molecular characterization of human tumors producing adrenocorticotropic hormone (ACTH). The main objectives include the analysis of transcriptome sequencing data, identification of differentially expressed genes, their functional analysis, and the search for chimeric genes. The research is based on transcriptome sequencing data, including 22 samples of ACTH-secreting pituitary adenomas, 6 samples of lung carcinoids, 1 sample of pancreatic neuroendocrine tumor, 7 samples of normal pituitary glands, and 8 samples of normal lung tissue. The methodology includes principal component analysis and differential gene expression analysis using DESeq2, gene ontology enrichment analysis with clusterProfiler. OncoboxPD was used for the analysis and interpretation of biological pathway activation levels. RNA-sequencing data deconvolution was performed using MuSiC. STAR-fusion was used for chimeric gene detection. ACTH-secreting samples demonstrated high heterogeneity in expression profiles. Increased activity in processes related to ion transport and changes in the structure of the extracellular matrix were observed. There was an increased activity in pathways related to cellular stress, metabolic adaptation, and cell migration, and decreased activity in pathways related to endocrine and neuronal functions. Lung carcinoid samples showed significant differences in expression profiles compared to controls. There was an increase in activity in processes related to neuroendocrine secretion and monoamine transport, and a decrease in processes related to interactions with the extracellular matrix. Six new chimeric genes not previously represented in databases were identified.