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.

中文翻译：

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丙酮酸脱氢酶激酶1在膀胱尿路上皮癌中的表达及预后意义。

肌浸润性膀胱尿路上皮癌（MIBC）是一种高度恶性的疾病，预后较差。根治性膀胱切除术是标准治疗方法。但是，由于手术和术后并发症，严重影响了患者的生活质量。因此，寻找MIBC的预后标志物和新的治疗靶标变得越来越重要。在这里，我们调查了PDK1，葡萄糖代谢的关键调节剂，在膀胱尿路上皮癌（BLCA）中的表达及其对预后的影响。通过生物信息学分析和免疫组织化学检查PDK1的表达模式。共选择101例BLCA的组织微阵列（TMA），其中包含肿瘤和成对的正常组织。我们证明了PDK1表达与我们的TMA队列中的肿瘤等级和Ki67表达相关（所有p值<0.05）。Kaplan-Meier生存分析显示，PDK1高表达的MIBC患者的预后要差于PDK1低表达的患者（p = 0.016）。多因素风险分析表明，PDK1表达增加是影响MIBC患者总体生存的独立预后因素。GSEA显示PDK1高表达表型差异性富集了mTOR途径，HIF途径，糖酵解，PI3K / AKT / mTOR信号传导等。因此，PDK1可能是MIBC的预后和治疗靶标。多因素风险分析表明，PDK1表达增加是影响MIBC患者总体生存的独立预后因素。GSEA表明，mTOR途径，HIF途径，糖酵解，PI3K / AKT / mTOR信号传导等在PDK1高表达表型中差异性富集。因此，PDK1可能是MIBC的预后和治疗靶标。多因素风险分析表明，PDK1表达增加是影响MIBC患者总体生存的独立预后因素。GSEA表明，mTOR途径，HIF途径，糖酵解，PI3K / AKT / mTOR信号传导等在PDK1高表达表型中差异性富集。因此，PDK1可能是MIBC的预后和治疗靶标。