文章：

膀胱癌的分子生物学：对发病机制和临床多样性的新认识

Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity

原文发布日期：2014-12-23

DOI: 10.1038/nrc3817

类型: Review Article

开放获取: 否

要点：

1. Bladder cancer is the fifth most common cancer in men in Western countries (male:female ratio is 3:1), and tobacco smoking is a major risk factor.
2. There are two major groups of patients with distinct prognosis and molecular features. Although local disease recurrence is a major problem for those with low-grade non-muscle-invasive tumours, life expectancy is long and development of invasive disease is infrequent. For those who present with muscle-invasive disease, development of metastatic disease is common, prognosis is dismal and no advances in therapy have been made for decades.
3. Major unmet clinical needs include non-invasive methods for disease surveillance and novel approaches to eliminate both tumour and widespread intraepithelial preneoplasia in patients with non-muscle-invasive disease. New systemic therapeutic approaches are urgently needed for those with muscle-invasive disease.
4. Recent studies reveal important biological features of urothelial metastasis and the epithelial–mesenchymal transition that may contribute to metastatic initiation. A key role for inflammatory processes is evident in the development of metastasis.
5. Heterogeneity in outcome within the two major groups indicates a need for subclassification for more accurate prognostication, prediction of response to current therapies and development of novel therapies.
6. Recent molecular analyses now provide such subclassification with definition of multiple subgroups that are independent of conventional histopathological definitions. This presents major opportunities for personalized patient care.

要点翻译：

1. 膀胱癌在西方国家是男性第五大常见癌症（男女比例为3:1），吸烟是其重要风险因素。
2. 该疾病主要分为两大患者群体，其预后和分子特征各不相同。虽然低级别非肌层浸润性肿瘤患者主要面临局部复发问题，但预期寿命较长且罕见进展为浸润性疾病。而对于肌层浸润性疾病患者，转移性病变发生率高、预后极差，且数十年来治疗方法未见突破。
3. 当前未满足的核心临床需求包括：针对非肌层浸润性疾病患者开发无创疾病监测手段及消除肿瘤与广泛上皮内瘤前病变的新策略；针对肌层浸润性疾病患者亟需新型全身治疗方案。
4. 最新研究揭示了尿路上皮转移的重要生物学特征，上皮-间质转化可能促进转移发生。炎症过程在转移发展中的关键作用已得到证实。
5. 两大类别内部的预后异质性提示需要进一步细分亚型，以实现更精准的预后判断、现有疗法疗效预测及新疗法开发。
6. 近期分子分析已建立此类亚分类体系，定义了多个独立于传统组织病理学分类的亚组，这为推进个体化诊疗提供了重要机遇。

英文摘要：

Urothelial carcinoma of the bladder comprises two long-recognized disease entities with distinct molecular features and clinical outcome. Low-grade non-muscle-invasive tumours recur frequently but rarely progress to muscle invasion, whereas muscle-invasive tumours are usually diagnosed de novo and frequently metastasize. Recent genome-wide expression and sequencing studies identify genes and pathways that are key drivers of urothelial cancer and reveal a more complex picture with multiple molecular subclasses that traverse conventional grade and stage groupings. This improved understanding of molecular features, disease pathogenesis and heterogeneity provides new opportunities for prognostic application, disease monitoring and personalized therapy.

摘要翻译： 

膀胱尿路上皮癌包含两种久已认知的疾病实体，具有不同的分子特征和临床结局。低级别非肌层浸润性肿瘤频繁复发，但很少进展为肌层浸润；而肌层浸润性肿瘤通常为新发诊断，且常发生转移。近期全基因组表达和测序研究识别了驱动尿路上皮癌的关键基因与通路，并揭示出更复杂的图景：存在多个跨越传统分级与分期界限的分子亚类。对分子特征、疾病发生机制及异质性的深入理解，为预后评估、疾病监测和个体化治疗提供了新的机遇。

原文链接：

Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity