Gene expression profiling of fast- and slow-growing non-functioning gonadotroph pituitary adenomas

Camilla Maria Falch, Arvind Y M Sundaram, Kristin Astrid Øystese, Kjersti Ringvoll Normann, Tove Lekva, Ivars Silamikelis, Alexander Kirkeby Eieland, Marianne Skovsager Andersen, Jens Bollerslev, Nicoleta Cristina Olarescu

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstrakt

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.

OriginalsprogEngelsk
TidsskriftEuropean Journal of Endocrinology
Vol/bind178
Udgave nummer3
Sider (fra-til)295-307
ISSN0804-4643
DOI
StatusUdgivet - mar. 2018

Bibliografisk note

© 2018 European Society of Endocrinology.

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