Lo Russo Giuseppe, Tessari Anna, Capece Marina, Galli Giulia, de Braud Filippo, Garassino Marina Chiara, Palmieri Dario
Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Department of Cancer Biology and Genetics, the Ohio State University, Columbus, OH, United States.
Front Oncol. 2018 Dec 21;8:650. doi: 10.3389/fonc.2018.00650. eCollection 2018.
Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with a variable incidence among different countries. Occupational asbestos exposure is the most important etiological factor and a very long latency period is widely reported. In the early phase of the disease, clinical signs are absent or not specific. For this reason, the diagnosis is frequently achieved only in the advanced stages. The histopathological diagnosis is also very complex, and no known factor can predict the prognosis with certainty. Nonetheless, current survival rates remain very low, despite the use of standard treatments, which include surgery, chemotherapy and radiotherapy. The identification of new prognostic and/or diagnostic biomarkers, and the discovery of therapeutic targets is a priority and could lead to a real significant impact on the management of malignant pleural mesothelioma. In this scenario, the role of microRNAs is becoming increasingly relevant, with the promise of a quick translation in the current clinical practice. Despite the relative novelty of this field, the number of works and candidate microRNAs that are present in literature is striking. Unfortunately, to date the microRNAs with the most clinical relevance for MPM are still matter of debate, probably due to the variety of approaches, techniques, and collected samples. Although specific microRNAs (e.g., let-7, miR-15 and miR-16, miR-21, miR-34a, and the miR-200 family) have been reported several times from different groups, the heterogeneity of published data reinforces the need of more comprehensive and unified studies on this topic. In this review we collect and discuss the studies focused on the involvement of microRNAs in different aspects of MPM, from their biological role in tumorigenesis and progression, to their possible application as diagnostic, prognostic and predictive biomarkers. Lastly, we examine their potential value as for the design of therapeutic approaches that could benefit MPM patients.
恶性胸膜间皮瘤（MPM）是一种罕见且侵袭性强的肿瘤，不同国家的发病率有所不同。职业性石棉暴露是最重要的病因，且普遍报道有很长的潜伏期。在疾病早期，临床症状不明显或不具有特异性。因此，诊断往往只能在晚期才能做出。组织病理学诊断也非常复杂，尚无已知因素能确切预测预后。尽管采用了包括手术、化疗和放疗在内的标准治疗方法，但目前的生存率仍然很低。识别新的预后和/或诊断生物标志物以及发现治疗靶点是当务之急，这可能会对恶性胸膜间皮瘤的治疗产生真正重大的影响。在这种情况下，微小RNA的作用变得越来越重要，有望在当前临床实践中迅速得到应用。尽管该领域相对较新，但文献中出现的相关研究和候选微小RNA数量惊人。不幸的是，迄今为止，对MPM具有最大临床相关性的微小RNA仍存在争议，这可能是由于方法、技术和收集样本的多样性所致。尽管不同研究小组多次报道了特定的微小RNA（如let-7、miR-15和miR-16、miR-21、miR-34a以及miR-200家族），但已发表数据的异质性强化了对该主题进行更全面和统一研究的必要性。在这篇综述中，我们收集并讨论了专注于微小RNA在MPM不同方面作用的研究，从它们在肿瘤发生和进展中的生物学作用，到它们作为诊断、预后和预测生物标志物的可能应用。最后，我们探讨了它们在设计可能使MPM患者受益的治疗方法方面的潜在价值。
