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Updated: Aug 14, 2026
Two-dimensional Gel Electrophoresis Coupled with Mass Spectrometry Methods for an Analysis of Human Pituitary Adenoma Tissue Proteome
Published on: April 2, 2018
Novel molecular signaling and classification of human clinically nonfunctional pituitary adenomas identified by gene
Carlos S Moreno1, Chheng-Orn Evans, Xianquan Zhan
1Department of Pathology and Laboratory Medicine and Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Abstract:
Pituitary adenomas comprise 10% of intracranial tumors and occur in about 20% of the population. They cause significant morbidity by compression of regional structures or the inappropriate expression of pituitary hormones. Their molecular pathogenesis is unclear, and the current classification of clinically nonfunctional tumors does not reflect any molecular distinctions between the subtypes. To further elucidate the molecular changes that contribute to the development of these tumors and reclassify them according to the molecular basis, we investigated 11 nonfunctional pituitary adenomas and eight normal pituitary glands, using 33 oligonucleotide GeneChip microarrays. We validated microarray results with the reverse transcription real-time quantitative PCR, using a larger number of nonfunctional adenomas. We also used proteomic analysis to examine protein expression in these nonfunctional adenomas. Microarray analysis identified significant increases in the expression of 115 genes and decreases in 169 genes, whereas proteomic analysis identified 21 up-regulated and 29 down-regulated proteins. We observed changes in expression of SFRP1, TLE2, PITX2, NOTCH3, and DLK1, suggesting that the developmental Wnt and Notch pathways are activated and important for the progression of nonfunctional pituitary adenomas. We further analyzed gene expression profiles of all nonfunctional pituitary subtypes to each other and identified genes that were affected uniquely in each subtype. These results show distinct gene and protein expression patterns in adenomas, provide new insight into the pathogenesis and molecular classification of nonfunctional pituitary adenomas, and suggest that therapeutic targeting of the Notch pathway could be effective for these tumors.
Insights
Pituitary adenomas, common intracranial tumors, have unclear molecular causes. This study reveals distinct gene and protein changes, highlighting the Wnt and Notch pathways
Area of Science:
- Neuro-oncology
- Molecular biology
- Genomics
Background:
- Pituitary adenomas represent 10% of intracranial tumors, causing morbidity through compression or hormone dysregulation.
- The molecular pathogenesis of pituitary adenomas, particularly nonfunctional subtypes, remains poorly understood.
- Current classification lacks molecular basis, hindering targeted therapies.
Purpose of the Study:
- To investigate molecular changes in nonfunctional pituitary adenomas.
- To reclassify nonfunctional pituitary adenomas based on molecular distinctions.
- To identify potential therapeutic targets for pituitary adenomas.
Main Methods:
- Oligonucleotide GeneChip microarrays were used to analyze gene expression in 11 nonfunctional pituitary adenomas and 8 normal pituitary glands.
- Reverse transcription quantitative PCR validated microarray findings in a larger cohort.
- Proteomic analysis examined protein expression in nonfunctional adenomas.
Main Results:
- Microarray analysis revealed significant differential expression of 115 upregulated and 169 downregulated genes.
- Proteomic analysis identified 21 upregulated and 29 downregulated proteins.
- Key genes involved in Wnt and Notch signaling pathways (SFRP1, TLE2, PITX2, NOTCH3, DLK1) showed altered expression, suggesting pathway activation.
Conclusions:
- Nonfunctional pituitary adenomas exhibit distinct gene and protein expression profiles.
- The Wnt and Notch signaling pathways are implicated in the progression of nonfunctional pituitary adenomas.
- Targeting the Notch pathway may offer a novel therapeutic strategy for these tumors.
