1. Gene expression profiling of fast- and slow-growing non-functioning gonadotroph pituitary adenomas.
- Author
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Falch CM, Sundaram AYM, Øystese KA, Normann KR, Lekva T, Silamikelis I, Eieland AK, Andersen M, Bollerslev J, and Olarescu NC
- Subjects
- Adaptor Proteins, Signal Transducing genetics, Adenoma metabolism, Adult, Aged, Cadherins genetics, Cell Adhesion Molecules genetics, Cell Movement genetics, Cyclic AMP-Dependent Protein Kinase Catalytic Subunits genetics, Female, Follicle Stimulating Hormone metabolism, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Silencing, Humans, In Vitro Techniques, Intracellular Signaling Peptides and Proteins genetics, Luteinizing Hormone metabolism, Male, Membrane Glycoproteins genetics, Membrane Proteins, Microtubule-Associated Proteins genetics, Middle Aged, Myosin Type I genetics, Nerve Tissue Proteins genetics, Pituitary Neoplasms metabolism, Proto-Oncogene Proteins genetics, Protocadherins, RNA-Binding Proteins, Receptors, Cell Surface genetics, Reverse Transcriptase Polymerase Chain Reaction, Ribonucleases genetics, Sialoglycoproteins genetics, Time Factors, Adenoma genetics, Epithelial-Mesenchymal Transition genetics, Pituitary Neoplasms genetics, RNA, Messenger metabolism
- Abstract
Objective: Reliable biomarkers associated with aggressiveness of non-functioning gonadotroph adenomas (GAs) are lacking. As the growth of tumor remnants is highly variable, molecular markers for growth potential prediction are necessary. We hypothesized that fast- and slow-growing GAs present different gene expression profiles and reliable biomarkers for tumor growth potential could be identified, focusing on the specific role of epithelial-mesenchymal transition (EMT)., Design and Methods: Eight GAs selected for RNA sequencing were equally divided into fast- and slow-growing group by the tumor volume doubling time (TVDT) median (27.75 months). Data were analyzed by tophat2, cufflinks and cummeRbund pipeline. 40 genes were selected for RT-qPCR validation in 20 GAs based on significance, fold-change and pathway analyses. The effect of silencing MTDH (metadherin) and EMCN (endomucin) on in vitro migration of human adenoma cells was evaluated., Results: 350 genes were significantly differentially expressed (282 genes upregulated and 68 downregulated in the fast group, P -adjusted <0.05). Among 40 selected genes, 11 showed associations with TVDT (-0.669< R <-0.46, P < 0.05). These were PCDH18, UNC5D, EMCN, MYO1B, GPM6A and six EMT-related genes ( SPAG9, SKIL, MTDH, HOOK1, CNOT6L and PRKACB ). MTDH , but not EMCN , demonstrated involvement in cell migration and association with EMT markers., Conclusions: Fast- and slow-growing GAs present different gene expression profiles, and genes related to EMT have higher expression in fast-growing tumors. In addition to MTDH , identified as an important contributor to aggressiveness, the other genes might represent markers for tumor growth potential and possible targets for drug therapy., (© 2018 European Society of Endocrinology.)
- Published
- 2018
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