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Eur J Endocrinol. 2018 Mar;178(3):295-307. doi: 10.1530/EJE-17-0702. Epub 2017 Dec 19.

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

Author information

1
Section of Specialized EndocrinologyDepartment of Endocrinology cafal14@student.sdu.dk.
2
Research Institute for Internal MedicineOslo University Hospital, Oslo, Norway.
3
Department of Endocrinology and MetabolismOdense University Hospital, Odense, Denmark.
4
University of Southern DenmarkOdense, Denmark.
5
Department of Medical GeneticsOslo University Hospital, Oslo, Norway.
6
Section of Specialized EndocrinologyDepartment of Endocrinology.
7
Faculty of MedicineUniversity of Oslo, Oslo, Norway.
8
Latvian Biomedical Research and Study Centre (LV BMC)Riga, Latvia.

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.

PMID:
29259037
DOI:
10.1530/EJE-17-0702
[Indexed for MEDLINE]

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