Browsing by Author "Gure, Ali Osmay"

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DNA Methylation of PI3K/AKT Pathway-Related Genes Predicts Outcome in Patients with Pancreatic Cancer: A Comprehensive Bioinformatics-Based Study
(MDPI, 2021-01-01) Faleiro, Ines; Roberto, Vania Palma; Demirkol Canli, Secil; Fraunhoffer, Nicolas A.; Iovanna, Juan; Gure, Ali Osmay; Link, Wolfgang; Castelo-Branco, Pedro
Simple Summary Pancreatic cancer is a highly lethal malignancy. Dysregulation of epigenetic mechanisms leads to abnormal patterns of gene expression contributing to the development and progression of cancer. We explored the ability of DNA methylation of PI3K-related genes to differentiate between malignant and healthy pancreatic tissue using distinct pancreatic cancer cohorts, and found that the methylation levels of the ITGA4, SFN, ITGA2, and PIK3R1 genes are altered in tumour samples since the early stages of malignant transformation and could serve as new diagnostic tools. We also demonstrate that these alterations correlate with overall survival and recurrence-free survival of the patients suggesting that its assessment can serve as independent prognostic indicators of patients' survival with higher sensitivity and specificity than the currently implemented biomarkers. Therefore, the methylation profile of genes involved in this pathway may be an alternative method for predicting cell malignancy and help doctors' decisions on patient care. Pancreatic cancer (PCA) is one of the most lethal malignancies worldwide with a 5-year survival rate of 9\%. Despite the advances in the field, the need for an earlier detection and effective therapies is paramount. PCA high heterogeneity suggests that epigenetic alterations play a key role in tumour development. However, only few epigenetic biomarkers or therapeutic targets have been identified so far. Here we explored the potential of distinct DNA methylation signatures as biomarkers for early detection and prognosis of PCA. PI3K/AKT-related genes differentially expressed in PCA were identified using the Pancreatic Expression Database (n = 153). Methylation data from PCA patients was obtained from The Cancer Genome Atlas (n = 183), crossed with clinical data to evaluate the biomarker potential of the epigenetic signatures identified and validated in independent cohorts. The majority of selected genes presented higher expression and hypomethylation in tumour tissue. The methylation signatures of specific genes in the PI3K/AKT pathway could distinguish normal from malignant tissue at initial disease stages with AUC > 0.8, revealing their potential as PCA diagnostic tools. ITGA4, SFN, ITGA2, and PIK3R1 methylation levels could be independent prognostic indicators of patients' survival. Methylation status of SFN and PIK3R1 were also associated with disease recurrence. Our study reveals that the methylation levels of PIK3/AKT genes involved in PCA could be used to diagnose and predict patients' clinical outcome with high sensitivity and specificity. These results provide new evidence of the potential of epigenetic alterations as biomarkers for disease screening and management and highlight possible therapeutic targets.
Epithelial-to-Mesenchymal Transition Is Not a Major Modulating Factor in the Cytotoxic Response to Natural Products in Cancer Cell Lines
(MDPI, 2021-01-01) Kucukkaraduman, Baris; Cicek, Ekin Gokce; Akbar, Muhammad Waqas; Canli, Secil Demirkol; Vural, Burcak; Gure, Ali Osmay
Numerous natural products exhibit antiproliferative activity against cancer cells by modulating various biological pathways. In this study, we investigated the potential use of eight natural compounds (apigenin, curcumin, epigallocatechin gallate, fisetin, forskolin, procyanidin B2, resveratrol, urolithin A) and two repurposed agents (fulvestrant and metformin) as chemotherapy enhancers and mesenchymal-to-epithelial (MET) inducers of cancer cells. Screening of these compounds in various colon, breast, and pancreatic cancer cell lines revealed anti-cancer activity for all compounds, with curcumin being the most effective among these in all cell lines. Although some of the natural products were able to induce MET in some cancer cell lines, the MET induction was not related to increased synergy with either 5-FU, irinotecan, gemcitabine, or gefitinib. When synergy was observed, for example with curcumin and irinotecan, this was unrelated to MET induction, as assessed by changes in E-cadherin and vimentin expression. Our results show that MET induction is compound and cell line specific, and that MET is not necessarily related to enhanced chemosensitivity.
Hypothetical molecular interconnection between type 2 diabetes and dyslexia
(BMC, 2021-01-01) Bulbul, Tugba; Baharlooie, Maryam; Safaeinejad, Zahra; Gure, Ali Osmay; Ghaedi, Kamran
Background Dyslexia is one of the most common learning disabilities, especially among children. Type 2 diabetes is a metabolic disorder that affects a large population globally, with metabolic disorders. There have been several genes that are identified as causes of Dyslexia, and in recent studies, it has been found out that some of those genes are also involved in several metabolic pathways. For several years, it has been known that type 2 diabetes causes several neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. Furthermore, in several studies, it was suggested that type 2 diabetes also has some associations with learning disabilities. This raises the question of whether ``Is there a connection between type 2 diabetes and dyslexia?{''}. In this study, this question is elaborated by linking their developmental processes via bioinformatics analysis about these two diseases individually and collectively. Result The literature review for dyslexia and type two diabetes was completed. As the result of this literature review, the genes that are associated to type 2 diabetes and dyslexia were identified. The biological pathways of dyslexia, and dyslexia associated genes, type 2 diabetes, and type 2 diabetes associated genes were identified. The association of these genes, regarding to their association with pathways were analysed, and using STRING database the gene associations were analysed and identified. Conclusion The findings of this research included the interaction analysis via gene association, co-expression and protein-protein interaction. These findings clarified the interconnection between dyslexia and type 2 diabetes in molecular level and it will be the beginning of an answer regarding to the relationship between T2D and dyslexia. Finally, by improving the understanding this paper aims to open the way for the possible future approach to examine this hypothesis.