Browsing by Author "Duran, Assist. Prof. Dr. Gizem Ayna"

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Bioinformatics Based Drug Repurposing Approach for Breast and Gynecological Cancers: RECQL4/FAM13C Genes Address Common Hub Genes and Drugs
(Galenos Publ House, 2025) Duran, Gizem Ayna; Duran, Assist. Prof. Dr. Gizem Ayna
Objective: 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.
Kolanjiyokarsinom ve Hepatoselüler Karsinom Hastalarında Farklı Genler Tarafından Tetiklenen Ortak Biyolojik Yolaklar
(2024) Ayna Duran, Gizem; Duran, Assist. Prof. Dr. Gizem Ayna
Kolanjiyokarsinom (CHOL) erken teşhis edilmesi zor olan ve oldukça yüksek düzeyde öldürücü bir kanser türüdür. CHOL tanısında radyolojik görüntülemede kısıtlılıklar mevcuttur ve biyopsi ile tanı yöntemi gibi invaziv tanı yöntemleri dışında genetik tabanlı ve özgün biyobelirteçlerin belirlenmesi zorunlu hale gelmektedir. Literatürde bu amaçlar gerçekleştirilen çalışmalar çalışmalardan farklı olarak bizim çalışmamızda öncelikle intrahepatik (iCHOL) ve ekstrahepatik (eCHOL) kolanjiyokarsinom hastalarında ortak upregüle olan genler belirlenmiştir. Ayrıca çalışmamızda klinikte CHOL kanserlerinin LIHC kanserinden ayırt edici tanısının zor olması sebebiyle CHOL hastalarında hepatoselüler karsinomdan (LICH) farklı olarak ve LIHC hastaları ile ortak olarak upregüle edilen genlerin tespit edilmesi de amaçlanmıştır. Hastaların gen yoğunluk verileri NCBI Gene Expression Omnibus (GEO) veri tabanından (GSE121248, GSE132305 ve GSE45001) sağlanmıştır. Çalışmada R LIMMA paketinde yer alan lineer modelleme yöntemi kullanılarak kanserli olan ve olmayan örnekler arasında upregüle genler (differentially expressed genes-DEGs) tespit edilmiştir. Tespit edilen genlerin hangi biyolojik yolaklara etki ettiğini belirlemek için Gen seti zenginleştirme analizi (Fonksiyonel zenginleştirme analizi) (GSEA) ShinyGO 0.80 webtool kullanılarak yapılmıştır. Sonuçlarımıza göre CHOL hastalarında LIHC hastalarından farklı olarak upregüle edilen 4 gene (F2R, ITGA11, LAMC2 ve LAMB3) odaklanılmıştır. CHOL ve LIHC hastalarında ise ortak olarak upregüle edilen 2 gen (COL1A1, ITGA2) tespit edilmiştir. Söz konusu genlerinin ortak olarak işaret ettiği biyolojik yolaklar PI3K-Akt sinyal yolağı ve ekstraselüler matriks (ECM)-reseptör etkileşimi süreçleridir. Belirlenen genler ile protein-protein ve ilaç etkileşim çalışmaları sonuçları klinik denemeler ile desteklenip CHOL ile LIHC kanserlerinin ayırt edilmesinde etkin bir şekilde hedeflenebilecektir.
Upregulated Acute Systemic Inflammation-Related Genes Based on Endotoxin Exposure Provide ‘Survival Benefit’ or Create ‘High Risk of Death’ in Leukaemia and Colon Cancer
(Istanbul University, 2024) Duran, Gizem Ayna; Duran, Assist. Prof. Dr. Gizem Ayna; Ayna Duran, Gizem
Objective: Although endotoxin exposure has been shown to trigger innate immune responses and promote cancer, it has also been shown to prevent cancer formation. In our study, survival analysis was performed to determine whether the upregulated genes triggered by endotoxins have hazardous effects on cancers or provide a survival benefit. Materials and Methods: Gene intensity values of control and bacterial endotoxin-administered individuals were obtained from the Gene Expression Omnibus database. Using the R "Linear Models for Microarray Data" package, differentially expressed gene analyses were conducted to determine genes that differ between healthy and bacterial endotoxin-administered samples. "ShinyGo 0.80" web-based tool was used to determine the disease types indicated by these genes. The "Kaplan-Meier Plotter" web-based tool was used to conduct survival analysis. Results: Genes that create an innate immune response to bacterial endotoxin exposure and are upregulated differently than in individuals without exposure were identified. According to gene enrichment analyses, the two main types of cancer identified were leukaemia/lymoma and colon cancer. We detected that MLF1, STAT5B, and BCL3 genes led to poor survival; however, the ARHGAP26 gene was protective for acute myeloid leukaemia patients. In the case of colon cancer, SMAD7 and TLR2 genes were determined as leading to "high risk of death". Conclusion: Once the systemic inflammation-related genes identified in our study are confirmed through laboratory experiments in samples taken from solid tissue in the case of colon cancer and at the level of genes obtained from blood samples in leukemias, genetically targeted treatments will also be possible.