Academic Journal
The expression pattern of pyruvate dehydrogenase kinases predicts prognosis and correlates with immune exhaustion in clear cell renal cell carcinoma
| العنوان: | The expression pattern of pyruvate dehydrogenase kinases predicts prognosis and correlates with immune exhaustion in clear cell renal cell carcinoma |
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| المؤلفون: | Nunes Xavier, Caroline E., Emaldi, Maite, Mingo Gómez de Oteo, Janire, Øyjord, Tove, Mælandsmo, Gunhild M., Fodstad, Øystein, Errarte Yarza, Peio, Larrinaga Embeita, Gorka, Llarena Ibarguren, Roberto, López, José I., Pulido Murillo, Rafael |
| بيانات النشر: | Nature |
| سنة النشر: | 2023 |
| المجموعة: | ADDI: Repositorio Institucional de la Universidad del País Vasco / Euskal Herriko Unibertsitatea (UPV/EHU - Basque Country University) |
| الوصف: | Renal cancer cells constitute a paradigm of tumor cells with a glycolytic reprogramming which drives metabolic alterations favouring cell survival and transformation. We studied the expression and activity of pyruvate dehydrogenase kinases (PDK1-4), key enzymes of the energy metabolism, in renal cancer cells. We analysed the expression, subcellular distribution and clinicopathological correlations of PDK1-4 by immunohistochemistry of tumor tissue microarray samples from a cohort of 96 clear cell renal cell carcinoma (ccRCC) patients. Gene expression analysis was performed on whole tumor tissue sections of a subset of ccRCC samples. PDK2 and PDK3 protein expression in tumor cells correlated with lower patient overall survival, whereas PDK1 protein expression correlated with higher patient survival. Gene expression analysis revealed molecular association of PDK2 and PDK3 expression with PI3K signalling pathway, as well as with T cell infiltration and exhausted CD8 T cells. Inhibition of PDK by dichloroacetate in human renal cancer cell lines resulted in lower cell viability, which was accompanied by an increase in pAKT. Together, our findings suggest a differential role for PDK enzymes in ccRCC progression, and highlight PDK as actionable metabolic proteins in relation with PI3K signalling and exhausted CD8 T cells in ccRCC. ; This work has been funded by Instituto de Salud Carlos III (ISCIII) through the projects CP20/00008 and PI22/00386, and co-funded by European Union, Stiftelsen til fremme av forskning innen nyresykdommer (Unifor 2021 and 2022), and NanoString Science Never Stop in the Nordics, nCounter Grant, to CENX. We thank Arantza Perez Dobaran (University of the Basque Country, UPV/EHU, Leioa, Bizkaia, Spain) for expert IHC technical support. We are grateful for the expert services provided on running the NanoString panels by the Helse Sør-Øst Genomics Core Facility at Oslo University Hospital. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2045-2322 |
| Relation: | https://www.nature.com/articles/s41598-023-34087-x; Scientific Reports 13 : (2023) // Article ID 7339; http://hdl.handle.net/10810/61932 |
| DOI: | 10.1038/s41598-023-34087-x |
| الاتاحة: | http://hdl.handle.net/10810/61932 https://doi.org/10.1038/s41598-023-34087-x |
| Rights: | info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/3.0/es/ ; © The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creativecommons. org/ licenses/ by/4. 0/ ; Atribución 3.0 España |
| رقم الانضمام: | edsbas.CD447DE3 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-023-34087-x |