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Two-dimensional Gel Electrophoresis Coupled with Mass Spectrometry Methods for an Analysis of Human Pituitary Adenoma Tissue Proteome
Published on: April 2, 2018
Epigenomic and transcriptomic landscaping unraveled candidate repositioned therapeutics for non-functioning pituitary
B Aydin1, H Beklen2, K Y Arga2,3
1Department of Bioengineering, Faculty of Engineering and Architecture, Konya Food and Agriculture University, Konya, Turkey.
Purpose:
Non-functioning pituitary neuroendocrine tumors are challengingly diagnosed tumors in the clinic. Transsphenoidal surgery remains the first-line treatment. Despite the development of state-of-the-art techniques, no drug therapy is currently approved for the treatment. There are also no randomized controlled trials comparing therapeutic strategies or drug therapy for the management after surgery. Therefore, novel therapeutic interventions for the therapeutically challenging NF-PitNETs are urgently needed.
Methods:
We integrated epigenome and transcriptome data (both coding and non-coding) that elucidate disease-specific signatures, in addition to biological and pharmacological data, to utilize rational pathway and drug prioritization in NF-PitNETs. We constructed an epigenome- and transcriptome-based PPI network and proposed hub genes. The signature-based drug repositioning based on the integration of multi-omics data was performed.
Results:
The construction of a disease-specific network based on three different biological levels revealed DCC, DLG5, ETS2, FOXO1, HBP1, HMGA2, PCGF3, PSME4, RBPMS, RREB1, SMAD1, SOCS1, SOX2, YAP1, ZFHX3 as hub proteins. Signature-based drug repositioning using hub proteins yielded repositioned drug candidates that were confirmed in silico via molecular docking. As a result of molecular docking simulations, palbociclib, linifanib, trametinib, eplerenone, niguldipine, and zuclopenthixol showed higher binding affinities with hub genes compared to their inhibitors and were proposed as potential repositioned therapeutics for the management of NF-PitNETs.
Conclusion:
The proposed systems' biomedicine-oriented multi-omics data integration for drug repurposing to provide promising results for the construction of effective clinical therapeutics. To the best of our knowledge, this is the first study reporting epigenome- and transcriptome-based drug repositioning for NF-PitNETs using in silico confirmations.
Insights
Novel drug candidates for non-functioning pituitary neuroendocrine tumors (NF-PitNETs) were identified by integrating multi-omics data. This study proposes repositioned drugs like palbociclib for NF-PitNETs management.
Area of Science:
- Endocrinology
- Oncology
- Computational Biology
Background:
- Non-functioning pituitary neuroendocrine tumors (NF-PitNETs) present diagnostic challenges.
- Current treatments lack approved drug therapies, necessitating novel interventions.
- Transsphenoidal surgery is the primary treatment, but post-surgical management options are limited.
Purpose of the Study:
- To identify novel therapeutic interventions for NF-PitNETs.
- To utilize multi-omics data for rational drug prioritization.
- To discover repositioned drug candidates for NF-PitNETs.
Main Methods:
- Integrated epigenome and transcriptome data (coding and non-coding) to identify disease-specific signatures.
- Constructed an epigenome- and transcriptome-based protein-protein interaction (PPI) network to identify hub genes.
- Performed signature-based drug repositioning using multi-omics data integration and in silico molecular docking.
Main Results:
- Identified key hub proteins including DCC, DLG5, ETS2, FOXO1, HBP1, HMGA2, PCGF3, PSME4, RBPMS, RREB1, SMAD1, SOCS1, SOX2, YAP1, and ZFHX3.
- Proposed drug candidates through signature-based repositioning, with palbociclib, linifanib, trametinib, eplerenone, niguldipine, and zuclopenthixol showing high binding affinities via molecular docking.
- Confirmed potential therapeutic efficacy of these drugs for NF-PitNETs management.
Conclusions:
- Multi-omics data integration offers a promising systems biomedicine approach for drug repurposing.
- This study is the first to report epigenome- and transcriptome-based drug repositioning for NF-PitNETs with in silico validation.
- The identified drug candidates represent potential novel therapeutics for NF-PitNETs.
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