Identification of Important Invasion-Related Genes in Non-functional Pituitary Adenomas

  • Harish Joshi
  • Basavaraj Vastrad
  • Chanabasayya VastradEmail author


Non-functioning pituitary adenomas (NFPAs) are locally invasive with high morbidity. The objective of this study was to diagnose important genes and pathways related to the invasiveness of NFPAs and gain more insights into the underlying molecular mechanisms of NFPAs. The gene expression profiles of GSE51618 were downloaded from the Gene Expression Omnibus database with 4 non-invasive NFPA samples, 3 invasive NFPA samples, and 3 normal pituitary gland samples. Differentially expressed genes (DEGs) are screened between invasive NFPA samples and normal pituitary gland samples, followed by pathway and ontology (GO) enrichment analyses. Subsequently, a protein–protein interaction (PPI) network was constructed and analyzed for these DEGs, and module analysis was performed. In addition, a target gene–miRNA network and target gene–TF (transcription factor) network were analyzed for these DEGs. A total of 879 DEGs were obtained. Among them, 439 genes were upregulated and 440 genes were downregulated. Pathway enrichment analysis indicated that the upregulated genes were significantly enriched in cysteine biosynthesis/homocysteine degradation (trans-sulfuration) and PI3K-Akt signaling pathway, while the downregulated genes were mainly associated with docosahexaenoate biosynthesis III (mammals) and chemokine signaling pathway. GO enrichment analysis indicated that the upregulated genes were significantly enriched in animal organ morphogenesis, extracellular matrix, and hormone activity, while the downregulated genes were mainly associated with leukocyte chemotaxis, dendrites, and RAGE receptor binding. Subsequently, ESR1, SOX2, TTN, GFAP, WIF1, TTR, XIST, SPAG5, PPBP, AR, IL1R2, and HIST1H1C were diagnosed as the top hub genes in the upregulated and downregulated PPI networks and modules. In addition, HS3ST1, GPC4, CCND2, and SCD were diagnosed as the top hub genes in the upregulated and downregulated target gene–miRNA networks, while CISH, ISLR, UBE2E3, and CCNG2 were diagnosed as the top hub genes in the upregulated and downregulated target gene–TF networks. The new important DEGs and pathways diagnosed in this study may serve key roles in the invasiveness of NFPAs and indicate more molecular targets for the treatment of NFPAs.


Non-functioning pituitary adenoma Gene ontology (GO) enrichment analysis Differentially expressed genes PPI network Modules 



The authors thank Jie Feng, Beijing Neurosurgical Institute, Tiantan Xili 6, Chongwen District, Beijing, China, very much, the author who deposited their microarray dataset, GSE51618, into the public GEO database.

Author Contributions

Harish Joshi collected important background information, Chanabasayya Vastrad performed R programming, statistical analysis, and software. Basavaraj Vastrad carried out the design of this study, performed the statistical analysis and visualizations, and drafted the manuscript.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed Consent

There is no informed consent because this study does not contain human or animal participants.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Endocrine and Diabetes Care CenterHubliIndia
  2. 2.Department of PharmaceuticsSET’S College of PharmacyDharwadIndia
  3. 3.Biostatistics and BioinformaticsDharwadIndia

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