Expression and prognostic significance of pyruvate dehydrogenase kinase 1 in bladder urothelial carcinoma
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ORIGINAL ARTICLE
Expression and prognostic significance of pyruvate dehydrogenase kinase 1 in bladder urothelial carcinoma Jinfeng Zhu 1 & Guihua Zheng 2 & Haifei Xu 1 & Xiaoxia Jin 2 & Ting Tang 3 & Xiaolin Wang 1 Received: 25 September 2019 / Revised: 17 February 2020 / Accepted: 21 February 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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. Keywords Pyruvate dehydrogenase kinase 1 . BLCA . IHC . TCGA . GSEA . Prognosis
Introduction Bladder urothelial carcinoma (BLCA) is one of the most common urinary malignancies threatening human health, with an estimated 549,400 new cases and 199,900 deaths worldwide Jinfeng Zhu and Guihua Zheng are co-first authors of this article. This article is part of the Topical Collection on Quality in Pathology Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00428-020-02782-z) contains supplementary material, which is available to authorized users. * Ting Tang [email protected] * Xiaolin Wang [email protected] 1
Department of Urology, Affiliated Tumor Hospital of Nantong University, Nantong 226361, Jiangsu, China
2
Department of Pathology, Affiliated Tumor Hospital of Nantong University, Nantong 226361, Jiangsu, China
3
Cancer Research Center Nantong, Tumor Hospital Affiliated to Nantong University, Nantong 226361, Jiangsu, China
in 2018 [1]. Nearly 25% of BLCA patients are diagnosed with the muscle invasive type (MIBC) [2]. According to the EAU guidelines, radical cystectomy is the standard treatment for MIBC [3]. However, due to the complications, trauma and decreased postoperative quality of life, some patients
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