Department of Health Sciences, Faculty of Medicine, University of Genoa, Genoa, Italy.
Ann N Y Acad Sci. 2012 Jul;1259:26-32. doi: 10.1111/j.1749-6632.2012.06646.x.
Chemoprevention is effective in inhibiting the onset of cancer in experimental animal models, but the transferability of similar results to humans is questionable. Therefore, reliable intermediate molecular biomarkers are needed to evaluate the efficacy of chemopreventive agents before the onset of cancer. The use of genomic biomarkers is limited by their poor predictive value. Although post-genomic biomarkers (i.e., gene-expression analyses) are useful for evaluating the safety, efficacy, and mechanistic basis of chemopreventive agents, the biomarkers are often poorly related to the phenotype, due to posttranscriptional regulation. Proteome analyses can evaluate preclinical phenotype alterations, but only at low protein counts. MicroRNA alterations, which are essential for the development of cancer, may be modulated by chemopreventive agents. Furthermore, microRNA delivery may be used to counteract carcinogenesis. Exposure to cigarette smoke induces microRNA let-7 downregulation and cell proliferation that can be converted to cell growth arrest and apoptosis upon let-7a transfection. Therefore, microRNAs are reliable biomarkers for evaluating chemoprevention efficacy and may be used to counteract carcinogenesis.
化学预防在抑制实验动物模型中癌症的发生方面是有效的，但类似结果在人类中的可转移性是有疑问的。因此，需要可靠的中间分子生物标志物来评估癌症发生前化学预防剂的疗效。基因组生物标志物的应用受到其预测价值差的限制。虽然后基因组生物标志物（即基因表达分析）可用于评估化学预防剂的安全性、功效和机制基础，但由于转录后调控，生物标志物通常与表型相关性较差。蛋白质组分析可评估临床前表型改变，但仅在低蛋白计数时才可行。微小 RNA 的改变对于癌症的发展至关重要，微小 RNA 的改变可能受到化学预防剂的调节。此外，微小 RNA 的传递可以用于对抗致癌作用。香烟烟雾的暴露会诱导微小 RNA let-7 的下调和细胞增殖，而微小 RNA let-7a 的转染可将其转化为细胞生长阻滞和细胞凋亡。因此，微小 RNA 是评估化学预防效果的可靠生物标志物，并且可以用于对抗致癌作用。
