Browsing by Author "Ergun, Cansu"

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Akut Miyeloid Lösemi'de Prognostik Genetik Belirteçlerin Belirlenmesi ve Yeni Terapötik Hedeflerin Keşfine Yönelik Biyoinformatik Yaklaşımlar
(2025) Ergun, Cansu; Duran, Gizem Ayna; Durmaz, Yağmur Kiraz
Akut miyeloid lösemi hematopoetik kök hücrelerin klonal çoğalmasıyla karakterize edilen heterojen bir kanser türüdür. Bu çalışma bu kanser türüne yeni ve özgün bir tedavi yöntemi önermek ve yeni hedeflenebilir çekirdek genleri belirlemeyi hedeflemiştir. Bu bağlamda, 615 AML hasta verisi ve 22 sağlıklı birey verisi açık veri tabanlarından elde edilmiştir. Elde edilen hasta verilerinin içerdiği 54,675 adet gen probu farklı ifade edilen gen analizi ve sağkalım analizi ile araştırılmıştır. Bu analizlere ise çekirdek gen analizleri eklenerek 4 adet çekirdek gen elde edilmiştir. Bu genler CCT5, ZBTB16, APP ve PTPN6 genleridir. Ortaya çıkarılan bu çekirdek genlere ek olarak önceki farklı ifade edilen gen analizlerinden ve farklı ifade edilen genlerin sağkalım analizlerinden elde edilen veri setleri ise özgün inhibe edici ilaçların belirlenmesi amacıyla ilaç yeniden konumlandırma ile LINCS L1000LCS veri tabanı kullanılarak analiz edildi ve hem farklı ifade edilen hem de farklı ifade edilen ve sağkalımı düşüren genler ayrı olmak üzere analiz edildi. Bu iki gen grubunun da inhibisyonunu sağlaması açısından önerilen 16-Hydroxytriptolide ve Tyrphostin AG-1478 ilaçları bu genlerin ifadesini tersine çevirme konusunda etkin bulunup potansiyel özgün ilaçlar olarak öne çıkmıştır. Ek olarak analizlerde ortaya çıkan Wortmannin, Parthenolide ve Vemurafenib ilaçları da potansiyel terapötikler olarak sunulmuştur. Bu çalışmanın bulguları yapılan biyoinformatik analizlerin ve yeni ortaya çıkacak hedefli tedavi opsiyonlarının önemini ve gelecek araştırmaların gerekliliğini ortaya koymaktadır.
Determination of Survival Associated Genetic Biomarkers To Discover Novel Therapeutic Targets for Acute Myeloid Leukaemia
(Taylor & Francis Ltd, 2025) Ergun, Cansu; Kiraz, Yagmur; Ayna Duran, Gizem
Acute myeloid leukemia (AML) is a heterogeneous malignancy specified by clonal proliferation of hematopoietic stem cells. This study identifies novel therapeutics for AML by integrating differential gene expression (DEG) and survival analyses. Publicly available GEO microarray datasets were analyzed, including data from 615 AML patients and 22 healthy controls. Multivariate Cox regression identified hazardous genes impacting survival. Protein-protein interaction networks using CytoScape revealed hub genes such as CCT5, ZBTB16, APP, and PTPN6. Functional enrichment revealed key AML-related pathways, such as PI3K/Akt and NF-kappaB signaling. Drug repurposing using the LINCS L1000CDS2 database highlighted potential therapeutics, including 16-Hydroxytriptolide and Tryptosthin AG-1478, with roles in reversing hazardous gene expression patterns. Additional candidates such as Vemurafenib, Parthenolide and Wortmannin, demonstrated promise as targeted agents. These findings underscore the potential of integrating bioinformatics and drug discovery to identify precision medicine in AML. Further studies are warranted to validate these targets and explore their clinical utility.
Exploring Pi3k Pathway Inhibitors for Acute Myeloid Leukemia: a Drug-Repurposing Approach
(Istanbul University Press, 2023) Ergun, Cansu; Kiremitci, Buse Zeren; Arslantas, Gizem; Bozkurt, Busenur; Duran, Gizem Ayna; Kiraz, Yağmur
Objective: 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.