Identification of driver genes and key pathways of non-functional pituitary adenomas predicts the therapeutic effect of STO-609

Objective Our study is to identify DEGs (Differentially Expressed Genes), comprehensively investigate hub genes, annotate enrichment functions and key pathways of Non-functional pituitary adenomas (NFPAs), and also to verify STO-609 therapeutic effect. Methods The gene expression level of NFPA and normal tissues were compared to identify the DEGs (Differential expressed genes) based on gene expression profiles (GSE2175, GSE26966 and GSE51618). Enrichment functions, pathways and key genes were identified by carrying out GO (Gene Ontology), KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis and PPI (Protein-Protein Interation) network analysis. Moreover, experiments in vitro were conducted to verify the anti-NFPAs effects of STO-609. Results 169 over-expression genes and 182 low expression genes were identified among 3 datasets. Dopaminergic synapse and vibrio cholerae infection pathways have distinctly changed in NFPA tissues. The Ca2+/CaM pathway played important roles in NFPA. Four hub proteins encoded by genes CALM1, PRDM10, RIPK4 and MAD2L1 were recognized as hub proteins. In vitro, assays showed that STO-609 induced apoptosis of NFPA cells to inhibit the hypophysoma cellular viability, diffusion and migration. Conclusion Four hub proteins, encoded by gene CALM1, PRDM10, RIPK4 and MAD2L1, played important roles in NFPA development. The Ca2+/CaM signaling pathway had significant alternations during NFPA forming process, the STO-609, a selective CaM-KK inhibitor, inhibited NFPA cellular viability, proliferation and migration. Meanwhile, NFPA was closely related to parkinson's disease (PD) in many aspects.