Amir Sharon, Mabjeesh Nicola J
Prostate Cancer Research Laboratory, Department of Urology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Histol Histopathol. 2017 Feb;32(2):107-119. doi: 10.14670/HH-11-814. Epub 2016 Sep 2.
Bladder cancer (BC) is generally divided into non-muscle-invasive BC (NMIBC) and muscle-invasive BC (MIBC). The standard treatment protocol for MIBC patients is radical cystectomy preceded by neoadjuvant chemotherapy (NAC). About one-half of the MIBC patients show a priori resistance to chemotherapy, and are therefore exposed to the risks of disease progression and toxicity from ineffective NAC. The discovery of microRNA (miRNA) regulation in tumorigenesis has provided new directions for the development of a new type of BC biomarkers. In this review, we describe the emerging miRNAs as BC biomarkers for different purposes, including diagnosis, prognosis and therapeutic response. miRNA expression profile changes with alteration of the tissue phenotype. This phenomenon is utilized to predict tumor diagnosis, cancer subclass, disease stage, prognosis and therapeutic response. We classified the miRNAs which are involved in bladder cancer according to malignant potential, chemoresistance, discrimination between normal to cancerous and clinical outcome. Focusing on the major obstacle regarding MIBC patient's NAC response, we summarized the miRNAs that are deregulated and have the potential to identify the patients resistant to NAC, such as miR-34, miR-100, miR-146b and miR-9 and miR-193a-3p. In conclusion, miRNAs expression profile of bladder cancer patient is a promising tool that can serve as biomarker for different aims. Based on this profile we propose upfront radical cystectomy instead of standard NAC to those MIBC patients who are at higher risk for chemoresistance and poor response.
膀胱癌(BC)一般分为非肌层浸润性膀胱癌(NMIBC)和肌层浸润性膀胱癌(MIBC)。MIBC患者的标准治疗方案是在新辅助化疗(NAC)后进行根治性膀胱切除术。约一半的MIBC患者对化疗呈现原发性耐药,因此面临疾病进展以及无效NAC带来的毒性风险。肿瘤发生过程中微小RNA(miRNA)调控的发现为新型BC生物标志物的开发提供了新方向。在本综述中,我们描述了新兴的miRNA作为用于不同目的的BC生物标志物,包括诊断、预后和治疗反应。miRNA表达谱随组织表型的改变而变化。这一现象被用于预测肿瘤诊断、癌症亚型、疾病分期、预后和治疗反应。我们根据恶性潜能、化疗耐药性、正常组织与癌组织的鉴别以及临床结果对参与膀胱癌的miRNA进行了分类。针对MIBC患者NAC反应的主要障碍,我们总结了失调且有可能识别对NAC耐药患者的miRNA,如miR-34、miR-100、miR-146b、miR-9和miR-193a-3p。总之,膀胱癌患者的miRNA表达谱是一种有前景的工具,可作为用于不同目的的生物标志物。基于这一表达谱,我们建议对那些化疗耐药风险较高且反应较差的MIBC患者直接进行根治性膀胱切除术,而非标准的NAC。