Profiling energy metabolism in normal bladder tissue and non-muscle-invasive bladder cancer cases of different histological grades

Tumor discovery Pub Date : 2024-03-19 DOI:10.36922/td.2290
Guilherme Prado Costa, Petra Karla Böckelmann, Renato Prado Costa, C. H. Schaal, Fernando César Sala, André Pereira Vanni, Leandro Luiz Lopes de Freitas, J. C. C. Alonso, G. Camargo, Gabriela de Oliveira, B. R. de Souza, A. Billis, Wagner José Fávaro
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Abstract

Bladder cancer (BC) stands as the second most common urinary tract malignancy. Recent years have witnessed a growing interest in investigating energy metabolism to help with better understanding the energy sources harnessed by tumor cells. The aims of the present study are to feature and compare cell energy metabolism profiles among different histological grades of non-muscle-invasive BC (NMIBC) by adjusting their bioenergetic cellular indexes based on the specific tumor types. Forty urinary bladder tissue samples from patients both with and without a diagnosis of urothelial lesions were collected. Subsequently, samples were categorized into four groups comprising ten samples each, namely: normal (no urothelial lesions) group, low-grade pTa group, high-grade pTa group, and high-grade pT1 group. These tissue samples were examined by means of immunohistochemistry and Western blotting to assess proteins involved in cell energy metabolism. Based on the current findings, the normal and low-grade pTa groups presented clear preference for the oxidative phosphorylation pathway; consequently, they recorded high bioenergetic cellular index. On the other hand, both the high-grade pTa and pT1 groups presented proclivity towards the glycolytic pathway. These observations, mainly those associated with the bioenergetic cellular index, hold promising clinical relevance in the management of BC. Given the often aggressive and potentially debilitating nature of treatments applied to this neoplasia type, the current study offers invaluable insights on this topic and emphasizes changes in the bioenergetic cellular index at different NMIBC grades, which could serve as potential markers for both the diagnosis and prognosis of NMIBC patients.
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正常膀胱组织和不同组织学级别的非肌层浸润性膀胱癌病例的能量代谢分析
膀胱癌(BC)是第二大常见的泌尿道恶性肿瘤。近年来,人们对研究能量代谢的兴趣与日俱增,这有助于更好地了解肿瘤细胞利用的能量来源。本研究的目的是根据具体的肿瘤类型调整非肌层浸润性膀胱癌(NMIBC)的生物能细胞指数,从而对不同组织学级别的非肌层浸润性膀胱癌(NMIBC)的细胞能量代谢特征进行分析和比较。研究人员收集了 40 份膀胱组织样本,这些样本分别来自确诊和未确诊为尿路上皮病变的患者。随后,样本被分为四组,每组十个样本,即正常(无尿道病变)组、低级别 pTa 组、高级别 pTa 组和高级别 pT1 组。这些组织样本通过免疫组化和 Western 印迹技术进行检测,以评估参与细胞能量代谢的蛋白质。根据目前的研究结果,正常组和低级 pTa 组明显偏好氧化磷酸化途径,因此它们的细胞生物能指数较高。另一方面,高级别 pTa 和 pT1 组都倾向于糖酵解途径。这些观察结果,主要是与生物能细胞指数相关的观察结果,对 BC 的临床治疗具有重要意义。鉴于对这种肿瘤类型的治疗往往具有侵袭性和潜在的削弱性,目前的研究为这一课题提供了宝贵的见解,并强调了不同 NMIBC 等级的生物能细胞指数的变化,这些变化可作为 NMIBC 患者诊断和预后的潜在标志物。
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