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This prospective controlled study established transcriptomic profiles of metabolism-related pathways in endometrial cancer using NanoString nCounter Technology (NanoString Metabolic Panel) on 57 tumors and 30 normal specimens, followed by qRT-PCR validation with very high similarity. Statistical analyses used GraphPad PRISM and Weka, identifying 11 deregulated genes linked to central carbon metabolism in cancer. 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nature.com/scientificreports)  \nOPEN  \nIdentification and subsequent validation of transcriptomic signature associated  \nwith metabolic status in endometrial cancer  \nIwona Sidorkiewicz1*, Maciej Jóźwik2, Angelika Buczyńska1, Anna Erol1, Marcin Jóźwik3, Marcin Moniuszko4,5, Katarzyna Jarząbek6, Magdalena Niemira1 & Adam Krętowski1,7  \nAberrant metabolism has been identified as a main driver of cancer. Profiling of metabolism-related pathways in cancer furthers the understanding of tumor plasticity and identification of potential metabolic vulnerabilities. In this prospective controlled study, we established transcriptomic profiles of metabolism-related pathways in endometrial cancer (EC) using a novel method, NanoString nCounter Technology. Fifty-seven ECs and 30 normal endometrial specimens were studied using the NanoString Metabolic Panel, further validated by qRT-PCR with a very high similarity. Statistical analyses were by GraphPad PRISM and Weka software. The analysis identified 11 deregulated genes (FDR ≤0.05; |FC|≥ 1.5) in EC: SLC7A11; SLC7A5; RUNX1; LAMA4; COL6A3; PDK1; CCNA1; ENO1; PKM; NR2F1; and NAALAD2 . Gene ontology showed direct association of these genes with ‘central carbon metabolism (CCM) in cancer’. Thus,‘CCM in cancer’ appears to create one of the main metabolic axes in EC. Further, transcriptomic data were functionally validated with drug repurposing on three EC cell lines, with several drug candidates suggested. These results lay the foundation for personalized therapeutic strategies in this cancer. Metabolic plasticity represents a promising diagnostic and therapeutic option in EC.  \nEndometrial cancer (EC) remains one of the most common cancers ofthe female reproductive system and its incidence is expected to rise sharply over the next decades1. Epidemiological and clinical evidence implicates metabolic abnormalities in its development2. However, the etiology of this disease is still debated. A categorization of EC involves two clinical types: Type I which encompasses endometrioid grade 1 (well differentiated) and grade 2 (moderately differentiated) tumors, and Type II: undifferentiated grade 3 of any histotype. Type I represents the vast majority (80–90%) of cases, especially in obese pre-, peri-, and early post-menopausal women, whereas Type II occurs mostly in postmenopausal women and has a high risk of relapse and metastatic disease3. Moreover, a new classification of EC by The Cancer Genome Atlas Consortium has been implemented, which considers four molecular subtypes. Molecular subtyping may yield information on cancer biology, prognosis and treatment benefits; however, a long-term follow-up is needed for the development of new management approaches4,5.  \nMetabolic reprogramming has been identified as one of the main drivers of cancer. Recent literature has established a molecular link between oncogenic pathways and tumor metabolism6. Cancer cells have an increased energy uptake and utilization compared with normal cells7 and prefer to convert glucose to pyruvate and lactate  \n1Clinical Research Centre, Medical University of Białystok, Marii Skłodowskiej-Curie 24a, 15-276 Białystok, Poland. 2Department of Gynecology and Gynecologic Oncology, Medical University of Białystok, 15-276 Białystok, Poland. 3Department of Gynecology and Obstetrics, Collegium Medicum, University of Warmia and Mazuryin Olsztyn, 10-045 Olsztyn, Poland. 4Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, 15-269 Białystok, Poland. 5Department of Allergology and Internal Medicine, Medical University of Bialystok, 15-276 Białystok, Poland. 6Laboratory of Genetic and Molecular Diagnostics, Maria Skłodowska-Curie Białystok Oncology Center, 15-027 Białystok, Poland. 7Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Białystok, 15-276 Białystok, Poland. *email: [iwona.sidorkiewicz@umb.edu.pl](iwona.sidorkiewicz@umb.","cbCainCcO9CW88NV","https://ap.wps.com/l/cbCainCcO9CW88NV","pdf",4098160,14,"English","# Metabolism-related transcriptomic changes in endometrial cancer and functional enrichment analysis\n## Study design and transcriptomic profiling\n## Differential genes and functional enrichment\n## Functional validation via drug repurposing\n## Background: endometrial cancer classification and metabolic reprogramming\n## Warburg effect and metabolic vulnerability\n## Study rationale and objectives","[{\"question\":\"What was the main goal of this study?\",\"answer\":\"To establish and validate a transcriptomic signature that characterizes the metabolic status in endometrial cancer and provides insight into related mechanistic pathways.\"},{\"question\":\"How were transcriptomic profiles measured and validated?\",\"answer\":\"Metabolism-related transcriptomic profiles were generated using NanoString nCounter Technology with the NanoString Metabolic Panel, then further validated by qRT-PCR with very high similarity.\"},{\"question\":\"Which metabolic pathway theme emerged from the gene analysis?\",\"answer\":\"Gene ontology analysis directly associated the deregulated genes with central carbon metabolism (CCM) in cancer, suggesting CCM as a key metabolic axis in endometrial cancer.\"}]","Identification and subsequent validation of transcriptomic signature associated with metabolic status in endometrial cancer | PDF",1790252112,35]