Amitriptyline; a systems biomedicine-oriented repositioned drug candidate for breast cancer

Download

HIBIT22_paper_75.pdf

Date

2022-10

Author

Taş, Fadime Dilşad
Okutan, Keziban
Ceylan, Tuğba
Özkaya, Ömer Faruk
Aydın, Büşra

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

208
views

51
downloads

Introduction: Breast cancer (BRCA) is a disease where the growth of breast cells is out of control. According to WHO’s latest cancer statistics, the BRCA is the world’s most prevalent cancer. In clinic, there are possible treatments that target cancer cells such as chemotherapy, radiation, or hormone therapies. However, these treatments have long-term side effects that can occur even multiple years after the treatment which may lead to even notorious consequences. Methods: Transcriptome-level BRCA gene expression profiling dataset with accession number GSE42568 was retrieved from GEO database and analyzed via GEO2R. Overall design of the dataset was consisting of 104 breast cancer biopsies and 17 healthy breast biopsies. As a result of gene expression analysis, differentially expressed genes (DEGs) were elucidated through p-value and FC cut-offs, which are 0.05 and 2, respectively. Consequently, the elucidation revealed 1540 DEGs in total which 788 of them upregulated and 752 of them down regulated. DEGs were functionally enriched via ConsensusPathDB. Biological network constructions around all DEGs were performed via protein-protein (BioGrid), miRNA gene (mirTarbase), and transcriptional factor gene interactions (TRRUST). These interaction networks were visualized via Cytoscape software and topological-network-analysis was performed using degree and betweenness-centrality metrics. Hubs of interaction networks were revealed and used further for survival and clustering analyses. The consequential results achieved through survival and clustering analyses were used to obtain repositioned drug candidates for BRCA via L1000CDS2 search engine. Results: As a result of functional-enrichment-analysis, antigen-processing and presentation, focal and cell adhesion pathways were significantly enriched. 50 drug candidates identified through drug repositioning based on transcriptional factor interaction, protein-protein interactions, and miRNA-level data combinations. Besides reporter signatures revealed from networks were utilized for determining relations of drugs to reverse observed changes in gene expression regarding BRCA. Potential of these drugs on BRCA was reviewed comprehensively through literature. The drug candidates were ranked according to 1-cos(α) search score. One of repositioned candidate drugs having highest score, amitriptyline, is used in clinic for treatment of migraine and depression. Discussion: We presented transcriptomic landscape of breast cancer through three-layered biological network including transcription factor-gene, protein-protein, and miRNA-gene interactions data combinations. Amitriptyline is proposed as repositioned drug, which will be further analyzed using BRCA cell lines, for management of BRCA based on transcriptome-based multi-level biological-network-interactions.

URI

https://hibit2022.ims.metu.edu.tr
https://hdl.handle.net/11511/101345

Conference Name

The International Symposium on Health Informatics and Bioinformatics

Collections

Graduate School of Informatics, Conference / Seminar

Suggestions

OpenMETU
Core

Targeting HIF1-alpha/miR-326/ITGA5 axis potentiates chemotherapy response in triple-negative breast cancer Assidicky, Ridho; Tokat, Unal Metin; Tarman, Ibrahim Oguzhan; Saatci, Ozge; Ersan, Pelin Gulizar; Raza, Umar; Ogul, Hasan; Riazalhosseini, Yasser; Can, Tolga; Sahin, Ozgur (2022-03-01) Purpose Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer that is frequently treated with chemotherapy. However, many patients exhibit either de novo chemoresistance or ultimately develop resistance to chemotherapy, leading to significantly high mortality rates. Therefore, increasing the efficacy of chemotherapy has potential to improve patient outcomes. Methods Here, we performed whole transcriptome sequencing (both RNA and small RNA-sequencing), coupled with network simu...
Multidrug resistance in logally advanced breast cancer Atalay, Mustafa Can; Gündüz, Ufuk; Department of Biotechnology (2004) Breast cancer is the most frequently detected cancer among women. Early diagnosis leads to long term survival when the patients are treated with surgery, radiotherapy, chemotherapy, and hormone therapy. Unfortunately, advanced disease could still be encountered in some patients resulting in a poorer prognosis. The primary treatment modality is chemotherapy for this group of patients. Drug resistance is a serious problem resulting in the use of different drugs during chemotherapy and knowing the possibility ...
Yhthesis, Antineoplastic Activity And Molecular Docking Studies Of Novel Indole- Thiazolidinedione Derivatives Kışla, Mehmet Murat; Zengin Karadayı, Fikriye; Doğan, Tuğba; Mutlu, Pelin; Alagöz, Zeynep (2021-06-22) Introduction: Cyclin-dependent kinase 6 (CDK6) became a valid target for breast cancer therapy over the past decades. Binding of this enzyme to E2F transcription factors eventually controls cell division. Therefore, inhibition of this enzyme becomes vital in apoptosis of the breast cancer cells. Besides, indole-thiazolidinediones prove to be a valuable asset in breast cancer therapy. The wide range of findings in this study area has encouraged us to design ...
Nuclear Deformability of Breast Cells Analyzed from Patients with Malignant and Benign Breast Diseases Antmen, Ezgi; Ermiş Şen, Menekşe; Kuren, Ozgur; Beksac, Kemal; Irkkan, Cigdem; HASIRCI, Vasıf Nejat (2023-03-13) Breast cancer is a heterogeneous and dynamic disease, in which cancer cells are highly responsive to alterations in the microenvironment. Today, conventional methods of detecting cancer give a rather static image of the condition of the disease, so dynamic properties such as invasiveness and metastasis are difficult to capture. In this study, conventional molecular-level evaluations of the patients with breast adenocarcinoma were combined with in vitro methods on micropatterned poly(methyl methacrylate) (PM...
miR-770-5p regulates EMT and invasion in TNBC cells by targeting DNMT3A Noyan, Senem; Andaç Özketen, Ayşe; Gurdal, Hakan; Gur Dedeoglu, Bala (2021-07-01) MicroRNAs (miRNAs) are shown to regulate various processes in cancer like motility and invasion that are key features of the metastatic triple negative breast cancer (TNBCs). Epithelial-mesenchymal transition (EMT) is one of the well-defined cellular transitioning processes characterized with reduced E-cadherin expression and increased mesenchymal molecules such as Vimentin or Snail thereby gives the cells mobility and invasive character. Aberrant DNA methylation by DNA methyltransferases (DNMTs) plays an i...

Citation Formats

F. D. Taş, K. Okutan, T. Ceylan, Ö. F. Özkaya, and B. Aydın, “Amitriptyline; a systems biomedicine-oriented repositioned drug candidate for breast cancer,” Erdemli, Mersin, TÜRKİYE, 2022, p. 3075, Accessed: 00, 2023. [Online]. Available: https://hibit2022.ims.metu.edu.tr.