Department of Gynecology and Obstetrics, University Hospital of Essen, Essen, Germany.
Clin Chem Lab Med. 2012 Jan 13;50(4):601-15. doi: 10.1515/cclm-2011-0847.
Ovarian cancer is the leading cause of death among gynecologic malignancies and despite advances in treatment, more than 50% of all patients will experience recurrence, resulting in worse overall prognosis. Therefore, identification of novel biomarkers for ovarian cancer is of significant interest. microRNA (miRNA) constitute a class of small gene regulatory RNA molecules (18-24 nt) and by sequence complementarity, they negatively regulate messenger RNA (mRNA) translation of target genes. Rising data are available that miRNA are functionally involved in the pathogenesis of ovarian cancer. In this regard, recent advances in profiling studies revealed a variety of miRNA candidates, differently expressed in ovarian carcinomas and in disease-specific conditions like hypoxia or chemo-resistance. This review abstracts recent efforts on establishing miRNA as novel molecular biomarkers for ovarian cancer and depicts the existing preliminary framework for defining peripheral-blood derived miRNA as novel circulating biomarkers. Beside these clinical implications, we highlight the current functional understanding of miRNA alteration and discuss major challenges in miRNA profiling approaches. Finally, we briefly outline methodologies to therapeutically modulate miRNA expression in cancer and try to assess how miRNA can improve our conceptual understanding and the clinical management of ovarian cancer.
卵巢癌是妇科恶性肿瘤死亡的主要原因,尽管治疗取得了进展,但超过 50%的患者将经历复发,导致总体预后更差。因此,寻找卵巢癌的新型生物标志物具有重要意义。microRNA(miRNA)是一类小的基因调控 RNA 分子(18-24 个核苷酸),通过序列互补性,它们负调控靶基因的信使 RNA(mRNA)翻译。越来越多的数据表明,miRNA 参与了卵巢癌的发病机制。在这方面,最近的基因表达谱研究进展揭示了多种 miRNA 候选物,它们在卵巢癌和特定疾病状态(如缺氧或化疗耐药)中表达不同。本文总结了 miRNA 作为卵巢癌新型分子生物标志物的最新研究进展,并描述了外周血衍生 miRNA 作为新型循环生物标志物的现有初步框架。除了这些临床意义外,我们还强调了目前对 miRNA 改变的功能理解,并讨论了 miRNA 表达谱分析方法中的主要挑战。最后,我们简要概述了治疗性调节癌症中 miRNA 表达的方法,并尝试评估 miRNA 如何改善我们对卵巢癌的概念理解和临床管理。