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Gene expression profiling of fast- and slow-growing non-functioning gonadotroph pituitary adenomas.
- Source :
- European Journal of Endocrinology; Mar2018, Vol. 178 Issue 3, p295-307, 13p
- Publication Year :
- 2018
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- GENE expression
GONADOTROPIN
ADENOMA
Subjects
Details
- Language :
- English
- ISSN :
- 08044643
- Volume :
- 178
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- European Journal of Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 128084166
- Full Text :
- https://doi.org/10.1530/EJE-17-0702