Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Dissecting the Metabolic Landscape of Breast Cancer Subtypes via Elastic Net Modeling and Examining Its Immune Correlates(Walter de Gruyter GmbH, 2026) Kus, M.E.; Ekiz, H.A.Objectives: Breast cancer is a heterogeneous disease, and the estrogen receptor (ER) status is a key factor in disease classification and treatment planning. While metabolomic profiling has revealed subtype-specific differences, cross-study comparisons have been limited, posing challenges for data extrapolation. This study aims to investigate metabolites that differentiate ER-positive and ER-negative tumors via integrative analyses of multi-omics data. Methods: We jointly analyzed two untargeted metabolomics datasets via elastic net modeling using consistent analysis pipelines tuned for low sample sizes, namely multiple bootstrapping and stability selection. Significant metabolite predictors from two studies were cross-examined to reveal distinctions and commonalities. We also performed differential gene expression analysis using RNA sequencing data from matching samples to link metabolic patterns with transcriptomic signatures and intratumoral immune cell signatures. Results: This study identified unique metabolite signatures in distinct datasets and a limited overlap of discriminating metabolites that can be broadly generalizable for subtyping. Nevertheless, several glycolysis and fatty acid metabolism intermediates exhibited variation depending on the tumor ER status. Consistently, genes related to fatty acid metabolism and glycolysis were enriched in ER-positive and ER-negative tumors respectively. Furthermore, we used multiple immune cell deconvolution algorithms to correlate various immune cell types with the metabolite levels within the tumor microenvironment. Conclusions: Together, these findings highlight the metabolic and immunological diversity of breast cancer and establish a reproducible machine-learning framework for integrating multi-omics data to interrogate tumor complexity. © 2025 the author(s), published by De Gruyter, Berlin/Boston.Article Subtype-Specific Divergent Roles of Calpain-1 and Calpain-2 in Basal a Triple-Negative Breast Cancer(BMC, 2025) Uner, Goklem; Oztarhan, Gokhan; Kirmizibayrak, Petek BallarBackgroundCAPN-1 and CAPN-2, two ubiquitously expressed calpains, have been implicated in cancer progression, but their distinct roles in breast cancer remain poorly defined. This study aims to define the opposing roles of CAPN-1 and CAPN-2 in breast cancer progression, with a focus on their regulatory impact on cell proliferation. Since these calpains may have different functions in the mammary gland, we aimed to investigate the possible antagonistic roles of CAPN-1 and CAPN-2 in breast cancer progression, focusing on their expression patterns and functional impact on cell proliferation.Methods and resultsWe analyzed breast cancer cell lines using immunoblotting and real-time cellular assays, showing that HCC1937 cells exhibit an opposite expression pattern of CAPN-1 and CAPN-2 compared to non-cancerous breast cells. CAPN-1 promoted cancer cell survival and negatively regulated CAPN-2 at both the protein and mRNA levels, whereas CAPN-2 suppressed proliferation. Additionally, the calpain activator AG-08 triggered cell death through CAPN-2 but not CAPN-1. In silico analysis confirmed higher CAPN-1 and lower CAPN-2 expression levels in breast cancer samples compared to normal tissue.ConclusionsThese findings indicate that CAPN-1 and CAPN-2 may exert antagonistic roles in breast cancer, but importantly, this effect was restricted to HCC1937 cells, representing a basal A TNBC subtype. Validation in additional basal A models and patient-derived samples will be essential to confirm these results. Our study, therefore, provides preliminary, model-specific insights into calpain regulation in TNBC and suggests that future therapeutic strategies should carefully account for subtype heterogeneity.Article Cx32 Cellular Localization Is Related To Epithelial To Mesenchymal Transition in Breast Cells(Pleiades Publishing inc, 2025) Oz, Sercan; Turan, Fatma Basak; Yondem, Eyup; Pesen-Okvur, Devrim; Yalcin-Ozuysal, Ozden; Ozcivici, Engin; Mese, GulistanConnexins (Cx) play both gap junction-related and -independent roles in cells, and their localization is essential for their function in cellular processes. Besides membrane localization, connexins can also be localized to the cytoplasm and nucleus, especially in cancer cells. The differential localization of connexins including Cx32 was observed in different stages of cancers. Cx32 was upregulated and observed in cytoplasms of cells in lymph-node metastasis of breast cancer samples compared to primary tumors. However, the significance of the increase in Cx32 expression and alteration of Cx32 cellular localization in epithelial-to-mesenchymal transition (EMT) is not known. To determine if Cx32 overexpression and/or localization over one week would induce the EMT process, we first examined the cellular localization of Cx32 in MCF10A and MDA-MB-231 cells at different time points using Western blot and RT-PCR as well as immunostaining with confocal microscopy. Then, we correlated the changes of Cx32 expression and localization with EMT marker expression. We showed that Cx32 had altered cellular localization and Cx32 overexpression increased Slug levels while it reduced E-cadherin and Snail expression in MDA-MB-231 for 7 days. In contrast, E-cadherin and Vimentin were reduced in MCF10A-Cx32 cells compared with controls over 7 days, and the expression pattern for nuclear Cx32 and Zeb2 was following similar pattern in MCF10A cells. Our results suggest a previously unknown time-dependent relation between Cx32 and the regulation of the EMT process.Article Long-Term Outcomes of Türkiye's First Population-Based Mammography Screening Program: a Decade of Breast Cancer Detection and Survival Analysis in Bahçeşehir(Bmc, 2025) Ozcinar, Beyza; Aribal, Erkin; Cabioglu, Neslihan; Gurdal, Sibel Ozkan; Varol, Gamze; Akyurt, Nuran; Ozmen, VahitBackgroundThe Bah & ccedil;e & scedil;ehir population-based mammography screening program (BMSP) is an example of T & uuml;rkiye's first population-based screening program. This study aims to reveal the successful implementation of population-based secreening program in one of the low- and middle-income countries, T & uuml;rkiye and long-term results of patients diagnosed with breast cancer during BMSP. MethodsThis study was conducted between 2009 and 2019, in the Bah & ccedil;e & scedil;ehir county of Istanbul. Women between the ages of 40 and 69 living in this region were invited every two years to undergo clinical breast examination (CBE) and mammography screening. All data was recorded in a dedicated software program. Women diagnosed with breast cancer were followed as a separate cohort. ResultsDuring the 10-year screening period, 8,825 women were screened and 146 (1.7%) breast cancers were detected. The median age at diagnosis for these patients was 52.9 years (40-69). The risk of breast cancer was 1.39 times higher (95% CI: 1.01-1.93) in women aged >= 50 compared to those less than 50 years (p = 0.045). The Cox regression analysis revealed that age at first birth, and number of births were significant predictors of breast cancer risk (p < 0.001, and p = 0.011). The breast cancer rate tends to increase as the breast density category progresses from A to D (p < 0.001). The median follow-up time for 146 breast cancer patients was 95.3 months. The 10-year breast cancer specific survival rate was 85%. ConclusionsThis study demonstrates that with a committed team and sufficient infrastructure, screening mammography can be effectively carried out in T & uuml;rkiye, leading to early detection and lower mortality rates. The recommended age to commence screening is 40 years old.Article Comprehensive Analysis Of<i> Gjb1</I> in Breast Cancer: Its Implications in Survival and Molecular Mechanisms(int inst Anticancer Research, 2024) Ozcivici, Engin; Mese, GulistanBackground/Aim: Breast cancer is the leading cause of cancer-related mortality among women worldwide. The connexin (Cx) family, including GJB1 (Cx32), plays complex roles in tumor progression depending on cellular context and cancer subtype. While Cx32 overexpression has been linked to lymph node metastasis, its effects on survival and molecular processes remain unclear. Herein, we aimed to investigate the role of GJB1 in breast cancer by examining its impact on survival and cellular processes in addition to its expression pattern in tumor subtypes, using public datasets. Materials and Methods: We conducted a comprehensive analysis of GJB1 in breast cancer using METABRIC patient dataset, Cancer Cell Line Encylopedia, and other publicly available databases. We examined the association between GJB1 expression and patient survival, performed differential gene expression analysis, and explored gene set enrichment to identify biological processes associated with high GJB1 expression. Results: GJB1 was significantly down-regulated in breast cancer tissues compared to normal tissues. However, patients with high GJB1 expression had significantly poorer survival compared to those with low expression, with the median survival reduced by over 25 months. Gene ontology (GO) analysis revealed that down- regulated genes in the GJB1-high group were enriched in extracellular matrix components and membrane junctions, while up-regulated genes were associated with mitochondrial function and cellular respiration. Conclusion: Our findings suggest a dual role for GJB1 in breast cancer. Although it is generally down-regulated, high GJB1 expression is associated with poorer survival, implying a potential oncogenic role. Further studies are needed to clarify the role of GJB1 in breast cancer and explore its therapeutic implications.Article Citation - WoS: 1Citation - Scopus: 1Comparison of Magnetic Seed and Rfid Methods in the Localization of Non-Palpable Breast Lesions(Wolters Kluwer Medknow Publications, 2024) Sanli, Ahmet Necati; Sanli, Deniz E. Tekcan; Golshan, Mehra; Sezgin, Efe; Celik, Varol; Aydogan, FatihBackground: Many methods have been developed for localizing non-palpable breast lesions. This study investigated the success rate and surgical results of the magnetic seed (Magseed) and radiofrequency identification (RFID) method, which are relatively new compared to standard wire-guided localizations. Materials and Methods: 20 simulation (10 Magseed, 10 RFID) models were created using turkey breasts and raisins. Raisins containing magnetic seed and RFID tags were placed on the turkey breast. Sentimag (R) probe was used for the Magseed group, and Faxitron LOCalizer (TM) System device was used in the RFID group. Both methods were evaluated in terms of accuracy in detecting breast lesion localization, operation times, excised tissue weights, total resection volume, surgical margin negativity, and re-excision rates. Results: Lesion localization success in both techniques was 100%. While procedure times were statistically significantly shorter in the Magseed group, incision lengths were shorter in the RFID group (P = 0.013, P = 0.007, respectively). No statistically significant difference was found between the groups for the weight of the removed parts, total resection volume, and surgical margin distance (P > 0.05). Conclusion: In this feasibility study, it was concluded that neither the RFID nor Magseed methods had a significant advantage over each other, in terms of localization detection and surgical margin negativity, and both methods could be used successfully for localization.