TR Dizin İndeksli Yayınlar Koleksiyonu / TR Dizin Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14365/4
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Article Bioinformatics Based Drug Repurposing Approach for Breast and Gynecological Cancers: RECQL4/FAM13C Genes Address Common Hub Genes and Drugs(Galenos Publ House, 2025-01-02) Duran, Gizem Ayna; Duran, Assist. Prof. Dr. Gizem AynaObjective: The prevalence of breast cancer and gynaecological cancers is high, and these cancer types can occur consecutively as secondary cancers. The aim of our study is to determine the genes commonly expressed in these cancers and to identify the common hub genes and drug components. Materials and Methods: Gene intensity values of breast cancer, gynaecological cancers such as cervical, ovarian and endometrial cancers were used from the Gene Expression Omnibus database Affymetrix Human Genome U133 Plus 2.0 Array project. Using the linear modelling method included in the R LIMMA package, genes that differ between healthy individuals and cancer patients were identified. Hub genes were determined using cytoHubba in Cytoscape program. “ShinyGo 0.80” tool was used to determine the disease-specific biological KEGG pathways. Drug.MATADOR from the ShinyGo 0.80 tool was used to predict drug-target relationships. Results: The RecQ Like Helicase 4 and Family with Sequence Similarity 13 Member C genes were found to be similarly expressed in breast cancer and gynaecological cancers. Upon KEGG pathway analyses with hub genes, Drug.MATADOR analysis with hub genes related to cancer related pathways was performed. We have determined these gene/drug interactions: NBN (targeted by Hydroxyurea), EP300 (targeted by Acetylcarnitine) and MAPK14 (targeted by Salicylate and Dibutyryl cyclic AMP). Conclusion: The drugs associated with hub genes determined in our study are not routinely used in cancer treatment. Our study offers the opportunity to identify the target genes of drugs used in breast and gynaecological cancers with the drug repurposing approach.Article Exploring Pi3k Pathway Inhibitors for Acute Myeloid Leukemia: a Drug-Repurposing Approach(Istanbul University Press, 2023-12-28) Ergun, Cansu; Kiremitci, Buse Zeren; Arslantas, Gizem; Bozkurt, Busenur; Duran, Gizem Ayna; Kiraz, YağmurObjective: Acute myeloid leukemia (AML) is a malignant disease characterized by the uncontrolled growth, differentiation, and proliferation of immature hematopoietic cells. Patients with AML often have poor survival rates, which are associated with specific gene mutations in FLT3, CEBPA, and NPM1. The phosphatidylinositol 3-kinase (PI3K) pathway, a lipase pathway, is activated in many malignancies, including AML. Given the low survival rates in AML, this study identified candidate drugs that could inhibit the PI3K pathway, thereby offering a potential treatment for AML, by using a drug-repurposing approach. Materials and Methods: Online bioinformatics tools were utilized to identify pathway-related genes and FDA-approved drugs. Subsequently, molecular docking was performed to determine the binding affinity values. Important genes were identified by evaluating their impact on survival and their aberrant expression in the tumor. In this study, genes such as VAV1, GSK3B, MTOR, PDPK1, PRR5, TSC2, AKT3, and CREB1 were determined and docked with their potential inhibitors. Particular attention was paid to VAV1 because there were no known potential VAV1 inhibitors used in AML. Results: The docking results were ranked, and the proposed gene–drug pairs were identified as tideglusib and fostamatinib for the inhibition of GSK3B, pimecrolimus and fostamatinib for the inhibition of MTOR, and fostamatinib for the inhibition of PDPK1. Furthermore, nebivolol, darifenacin, dihydroergotamine, libanserin and entereg were identified as potential inhibitors of VAV1 in AML. Conclusion: To sum up, most effective gene–drug pairs according to binding affinities were proposed as candidate inhibitor drugs for AML.Article Determination of Eight Hub Genes and Functional Pathways Affecting Both the Survival of Early- and Late-Stage Colon Cancer Patients(Kare Publ, 2023) Ayna Duran, Gizem; Sert, Fatma; Duran, Assist. Prof. Dr. Gizem Ayna; Duran, Gizem AynaOBJECTIVEThe stage of colon cancer (CC) and therefore the level at which the treatment is initiated affects the survival of CC patients. In our study, we aimed to identify the common survival-related genes in both early-and late-stage CC patients.METHODSInformation on the demographic characteristics of 581 patients and microarray expression profiles (GSE39582) were obtained from the gene expression omnibus database. Survival analysis was per-formed using univariate and multivariate Cox regression methods with the help of R3.53 programming language and Kaplan-Meier graphics through the R software Survival package. ShinyGO v0.741 gene ontology enrichment analysis was performed to clarify the common and functional pathways related to both early-and late-stage CC cancer patients' data.RESULTSCox regression analysis indicated that overall survival and relapse-free survival of CC patients were strongly influenced by stage. Genes that significantly affect prognosis and survival in early-and late -stage CC patients were identified. As a result of gene enrichment analysis, arginine binding, oxidore-ductase activity, and methylcytosine dioxygenase activity and related eight hub genes (TM4SF5, NOS3, Ten eleven translocation [TET1], TET3, JMJD7, AKR1C1, prenylcysteine oxidase 1 like, Methionine sulfoxide reductase A) were identified.CONCLUSIONAccording to our results, it might be considered that developing new treatment strategies based on eight hub-genes related to arginine binding, oxidoreductase activity, and methylcytosine dioxygenase activity detected at different stages of CC might increase the success of targeted therapies.