Molecular biomarkers of progression in non-muscle-invasive bladder cancer — beyond conventional risk stratification

IF 12.1 1区 医学 Q1 UROLOGY & NEPHROLOGY Nature Reviews Urology Pub Date : 2024-08-02 DOI:10.1038/s41585-024-00914-7
Mitchell Olislagers, Florus C. de Jong, Vera C. Rutten, Joost L. Boormans, Tokameh Mahmoudi, Tahlita C. M. Zuiverloon
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Abstract

The global incidence of bladder cancer is more than half a million diagnoses each year. Bladder cancer can be categorized into non-muscle-invasive bladder cancer (NMIBC), which accounts for ~75% of diagnoses, and muscle-invasive bladder cancer (MIBC). Up to 45% of patients with NMIBC develop disease progression to MIBC, which is associated with a poor outcome, highlighting a clinical need to identify these patients. Current risk stratification has a prognostic value, but relies solely on clinicopathological parameters that might not fully capture the complexity of disease progression. Molecular research has led to identification of multiple crucial players involved in NMIBC progression. Identified biomarkers of progression are related to cell cycle, MAPK pathways, apoptosis, tumour microenvironment, chromatin stability and DNA-damage response. However, none of these biomarkers has been prospectively validated. Reported gene signatures of progression do not improve NMIBC risk stratification. Molecular subtypes of NMIBC have improved our understanding of NMIBC progression, but these subtypes are currently unsuitable for clinical implementation owing to a lack of prospective validation, limited predictive value as a result of intratumour subtype heterogeneity, technical challenges, costs and turnaround time. Future steps include the development of consensus molecular NMIBC subtypes that might improve conventional clinicopathological risk stratification. Prospective implementation studies of biomarkers and the design of biomarker-guided clinical trials are required for the integration of molecular biomarkers into clinical practice.

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非肌层浸润性膀胱癌进展的分子生物标志物--超越传统的风险分层方法
全球每年确诊的膀胱癌患者超过 50 万。膀胱癌可分为非肌层浸润性膀胱癌(NMIBC)和肌层浸润性膀胱癌(MIBC),前者约占确诊病例的 75%。多达 45% 的非肌肉浸润性膀胱癌患者会发展为肌肉浸润性膀胱癌,这与不良预后有关,因此临床上需要识别这些患者。目前的风险分层具有预后价值,但仅靠临床病理参数可能无法完全反映疾病进展的复杂性。分子研究已经发现了多个参与 NMIBC 进展的关键因素。已确定的疾病进展生物标志物与细胞周期、MAPK 通路、细胞凋亡、肿瘤微环境、染色质稳定性和 DNA 损伤反应有关。然而,这些生物标志物都没有经过前瞻性验证。已报道的进展基因特征并不能改善 NMIBC 的风险分层。NMIBC 的分子亚型提高了我们对 NMIBC 进展的认识,但由于缺乏前瞻性验证、瘤内亚型异质性导致预测价值有限、技术挑战、成本和周转时间等原因,这些亚型目前还不适合临床应用。未来的研究步骤包括开发可改善传统临床病理学风险分层的 NMIBC 共识分子亚型。需要对生物标记物进行前瞻性实施研究,并设计以生物标记物为指导的临床试验,以便将分子生物标记物纳入临床实践。
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来源期刊
Nature Reviews Urology
Nature Reviews Urology 医学-泌尿学与肾脏学
CiteScore
12.50
自引率
2.60%
发文量
123
审稿时长
6-12 weeks
期刊介绍: Nature Reviews Urology is part of the Nature Reviews portfolio of journals.Nature Reviews' basic, translational and clinical content is written by internationally renowned basic and clinical academics and researchers. This journal targeted readers in the biological and medical sciences, from the postgraduate level upwards, aiming to be accessible to professionals in any biological or medical discipline. The journal features authoritative In-depth Reviews providing up-to-date information on topics within a field's history and development. Perspectives, News & Views articles, and the Research Highlights section offer topical discussions and opinions, filtering primary research from various medical journals. Covering a wide range of subjects, including andrology, urologic oncology, and imaging, Nature Reviews provides valuable insights for practitioners, researchers, and academics within urology and related fields.
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