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组织和可溶性 microRNAs 在消化道癌症的诊断和治疗中的作用。

Tissular and soluble miRNAs for diagnostic and therapy improvement in digestive tract cancers.

机构信息

National Institute for Chemical Pharmaceutical R&D, 112 Vitan Ave, 031299, Bucharest, Romania.

出版信息

Expert Rev Mol Diagn. 2011 Jan;11(1):101-20. doi: 10.1586/erm.10.106.

DOI:10.1586/erm.10.106
PMID:21171925
Abstract

Digestive cancers (e.g., gastric, colorectal, pancreatic or hepatocarcinoma) are among the most frequently reported cancers in the world, and are characterized by invasivity, metastatic potential and poor outcomes. This group includes some of the most critical cancers (among them, are those ranked second to forth in cancer-related mortality) and, despite all sustained efforts, they maintain a profile of low survival rates and lack successful therapies. Discovery of biomarkers that improve disease characterization may make optimized or personalized therapy possible. Novel biomarkers are expected to provide, hopefully, less-invasive or noninvasive diagnostic tools that make possible earlier detection of disease. Also, they may provide a more reliable selection instrument in the drug discovery process. miRNAs, short noncoding RNAs, have emerged in the last few years as significant regulators of cellular activities, controlling protein expression at the post-transcriptional level, with a significant implication in pathology in general and, of most relevance, in cancers. Deregulation of miRNA expression levels and some genetic alterations were demonstrated in various cancers, including digestive cancers. Investigations in tissue samples have provided a considerable amount of knowledge, identifying altered expressions of miRNAs associated with tumorigenesis and tumor progression. Overexpression of some tumor-inducing or tumor-promoting miRNAs was demonstrated, as well as the downregulation of tumor-suppressor miRNAs. Both individual miRNAs, as well as sets of multiple miRNAs, were set up as candidate biomarkers for diagnostics or monitoring, offering relevant insights into tumorigenic mechanisms. Circulating miRNAs were demonstrated as valuable instruments in tumor diagnosis and the prognosis of digestive cancers (affecting the esophagus, stomach, intestine, colorectum, liver and pancreas), and are being investigated thoroughly in order to generate and validate less-invasive diagnostic tools with enhanced sensitivity.

摘要

消化系统癌症(例如胃癌、结直肠癌、胰腺癌或肝癌)是世界上最常见的癌症之一,其特征为侵袭性、转移性和预后不良。这组癌症包括一些最严重的癌症(其中包括癌症相关死亡率排名第二至第四的癌症),尽管我们一直在努力,但它们的生存率仍然很低,缺乏有效的治疗方法。发现能够改善疾病特征的生物标志物可能使优化或个性化治疗成为可能。新的生物标志物有望提供更具侵入性或非侵入性的诊断工具,从而更早地发现疾病。此外,它们还可能为药物发现过程提供更可靠的选择工具。

miRNAs 是短的非编码 RNA,在过去几年中作为细胞活动的重要调节剂出现,在转录后水平控制蛋白质表达,对一般病理学具有重要意义,尤其是对癌症具有重要意义。在各种癌症中,包括消化系统癌症,已经证明了 miRNA 表达水平的失调和一些遗传改变。对组织样本的研究提供了大量的知识,确定了与肿瘤发生和肿瘤进展相关的 miRNA 的改变表达。一些诱导肿瘤或促进肿瘤的 miRNA 的过表达,以及肿瘤抑制 miRNA 的下调都被证明了。单个 miRNA 以及多 miRNA 集都被作为诊断或监测的候选生物标志物,为肿瘤发生机制提供了有价值的见解。

循环 miRNA 被证明是消化系统癌症(影响食管、胃、肠、结肠直肠、肝和胰腺)诊断和预后的有价值工具,正在进行深入研究,以开发和验证具有增强敏感性的非侵入性诊断工具。

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