
MICROARRAY TECHNOLOGY REVEALS POTENTIALLY
NOVEL GENES AND PATHWAYS INVOLVED IN
NON-FUNCTIONING PITUITARY ADENOMAS Qiao X, Wang H, Wang X, Zhao B, Liu J, *Corresponding Author: Jun Liu, M.D., Department of Neurosurgery, The Second Hospital of Jilin University, 218 Ziqiang
Road, Changchun, 130021, Jilin Province, People’s Republic of China. Tel: +86-138-0431-7080. E-mail: LiuJun66@126.com page: 5
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RESULTS
Differentially Expressed Genes and Clusters. A
total of 604 DEGs were acquired between NFPAs and
controls, involving 177 up- and 427 down-regulated genes.
The top 10 up-regulated genes and top 10 down-regulated
genes are shown in Table 1. The 604 DEGs and 23 samples
were clustered, and DEGs could well differentiate the
disease samples from the healthy controls (Figure 1).
Functions and Pathways. The GO enrichment analysis
and KEGG pathway analysis were performed to reveal
the key biological functions altered in NFPAs. As shown
in Table 2, 12 pathways were significantly enriched, which were mainly associated with signaling pathway and receptor
interaction. In GO enrichment analysis, DEGs were
significantly enriched in 1037 biological process terms
mainly about cell communication and signaling, 65 cellular
component terms mainly related with an extracellular
matrix (ECM), plasma membrane, and collagen, as well
as 186 molecular function terms mainly associated with
transcription factor activity and receptor binding (Table
2). In order to better understand the positions of DEGs in
pathways and their roles in the development of NFPAs,
we visualized four significant pathways that had been reported
to participate in the pathogenesis of NFPAs or PAs,
including MAPK signaling pathway [10] (Figure 2), p53
signaling pathway [24] (Figure 3), transforming growth
factor β (TGFβ), signaling pathway [25] (Figure 4), and
Jak-STAT signaling pathway [8] (Figure 5).
Protein-Protein Interaction Network of Differentially
Expressed Genes. For the 604 DEGs, the PPI
network was constructed using information from STRING
v10 (Figure 6). The whole network consisted of 115 upregulated
DEGs, 305 down-regulated DEGs and 1379
PPIs (Figure 6).
Potential Novel Non-Functioning Pituitary Adenoma-
Related Genes and Sub-Network. Known disease
genes were obtained from the CTD database (http://ctdbase.org/) and compared with the DEGs in the PPI network.
Consequently, 99 up- and 288 down-regulated DEGs
were known disease genes, e.g. EGFR (epidermal growth
factor receptor, degree = 63) [10,26-28] and ESR1 (estrogen
receptor 1, degree = 48) [29] (Figure 6). In contrast,
16 up- and 17 down-regulated DEGs were potential novel
NFPA-related genes, e.g. COL4A5 (collagen type IV α5,
degree = 17), LHX3 (LIM homeobox protein 3, degree
= 11), MSN (moesin, degree = 11) and GHSR (growth
hormone secretagogue receptor, degree = 10) (Figure 6).
Moreover, COL4A5 interacted with known NFPA-related
genes such as EGFR, LHX3 interacted with known NFPAsrelated
genes like PRL (Prolactin), and MSN interacted
with known NFPA-related genes such as EGFR. Among
the top 10 up-regulated genes and top 10 down-regulated
genes, only 12 DEGs interacted with other DEGs [e.g. CDKN2A
(cyclin-dependent kinase inhibitor 2A)-IDH1 (isocitrate
dehydrogenase 1)], and all 12 DEGs were known
disease genes [e.g. DLK1 (δ-like 1 homologue)] (Figure 7).
In addition, potential NFPA-related gene GHSR interacted
with the top DEG GH1 (growth hormone 1).
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