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Expression and prognostic significance of pyruvate dehydrogenase kinase 1 in bladder urothelial carcinoma

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Abstract

Muscular infiltrating bladder urothelial carcinoma (MIBC) is a highly malignant disease with a poor prognosis. Radical cystectomy is the standard treatment. However, due to surgery and postoperative complications, the quality of life of patients is seriously affected. Therefore, it is increasingly important to find prognostic markers and new therapeutic targets for MIBC. Here, we investigated the expression of PDK1, a key regulator of glucose metabolism, in bladder urothelial carcinoma (BLCA) and its effect on prognosis. The expression pattern of PDK1 was examined by bioinformatics analysis and immunohistochemistry. A total of 101 cases of BLCA were selected for tissue microarrays (TMAs) that contained both tumour and paired normal tissues. We demonstrated that PDK1 expression was correlated with tumour grade and Ki67expression in our TMA cohort (all p values < 0.05). Kaplan-Meier survival analysis showed that patients with MIBC with high PDK1 expression had a worse prognosis than patients with low PDK1 expression (p = 0.016). Multifactor risk analysis showed that increased PDK1 expression was an independent prognostic factor affecting the overall survival of MIBC patients. GSEA showed that the mTOR pathway, HIF pathway, glycolysis, PI3K/AKT/mTOR signalling, etc. were differentially enriched in the PDK1 high expression phenotype. Hence, PDK1 may be a prognostic and therapeutic target for MIBC.

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Funding

Our work was granted by Jiangsu Provincial Commission of Health and Family Planning (H201663) and the Project of Science and Technology Bureau of Nantong (MS22019010).

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Authors and Affiliations

  1. Department of Urology, Affiliated Tumor Hospital of Nantong University, Nantong, 226361, Jiangsu, China

    Jinfeng Zhu, Haifei Xu & Xiaolin Wang

  2. Department of Pathology, Affiliated Tumor Hospital of Nantong University, Nantong, 226361, Jiangsu, China

    Guihua Zheng & Xiaoxia Jin

  3. Cancer Research Center Nantong, Tumor Hospital Affiliated to Nantong University, Nantong, 226361, Jiangsu, China

    Ting Tang

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  1. Jinfeng Zhu
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  2. Guihua Zheng
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  3. Haifei Xu
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  4. Xiaoxia Jin
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  5. Ting Tang
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  6. Xiaolin Wang
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Contributions

All authors read and approved the final manuscript prior to submission. T.T. and X.W. designed research, analysed data and provided funding. H.X. provided clinical data; Z.F. performed experiments, analysed data and wrote the manuscript; G.Z. and X.J. performed IHC analysis.

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Correspondence to Ting Tang or Xiaolin Wang.

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Jinfeng Zhu and Guihua Zheng are co-first authors of this article.

This article is part of the Topical Collection on Quality in Pathology

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Zhu, J., Zheng, G., Xu, H. et al. Expression and prognostic significance of pyruvate dehydrogenase kinase 1 in bladder urothelial carcinoma. Virchows Arch 477, 637–649 (2020). https://doi.org/10.1007/s00428-020-02782-z

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  • DOI: https://doi.org/10.1007/s00428-020-02782-z

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