Anglim Paul P, Alonzo Todd A, Laird-Offringa Ite A
Departments of Surgery and of Biochemistry and Molecular Biology, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089-9176, USA.
Mol Cancer. 2008 Oct 23;7:81. doi: 10.1186/1476-4598-7-81.
Lung cancer is the number one cancer killer in the United States. This disease is clinically divided into two sub-types, small cell lung cancer, (10-15% of lung cancer cases), and non-small cell lung cancer (NSCLC; 85-90% of cases). Early detection of NSCLC, which is the more common and less aggressive of the two sub-types, has the highest potential for saving lives. As yet, no routine screening method that enables early detection exists, and this is a key factor in the high mortality rate of this disease. Imaging and cytology-based screening strategies have been employed for early detection, and while some are sensitive, none have been demonstrated to reduce lung cancer mortality. However, mortality might be reduced by developing specific molecular markers that can complement imaging techniques. DNA methylation has emerged as a highly promising biomarker and is being actively studied in multiple cancers. The analysis of DNA methylation-based biomarkers is rapidly advancing, and a large number of potential biomarkers have been identified. Here we present a detailed review of the literature, focusing on DNA methylation-based markers developed using primary NSCLC tissue. Viable markers for clinical diagnosis must be detectable in 'remote media' such as blood, sputum, bronchoalveolar lavage, or even exhaled breath condensate. We discuss progress on their detection in such media and the sensitivity and specificity of the molecular marker panels identified to date. Lastly, we look to future advancements that will be made possible with the interrogation of the epigenome.
肺癌是美国头号癌症杀手。这种疾病在临床上分为两种亚型，小细胞肺癌（占肺癌病例的10 - 15%）和非小细胞肺癌（NSCLC；占病例的85 - 90%）。NSCLC是两种亚型中更常见且侵袭性较小的一种，早期检测具有最高的挽救生命潜力。然而，目前尚无能够实现早期检测的常规筛查方法，这是该疾病高死亡率的一个关键因素。基于成像和细胞学的筛查策略已被用于早期检测，虽然有些方法具有敏感性，但尚无证据表明这些方法能降低肺癌死亡率。不过，通过开发可补充成像技术的特定分子标志物，死亡率可能会降低。DNA甲基化已成为一种极具前景的生物标志物，并且正在多种癌症中进行积极研究。基于DNA甲基化的生物标志物分析正在迅速发展，大量潜在生物标志物已被识别。在此，我们对文献进行详细综述，重点关注使用原发性NSCLC组织开发的基于DNA甲基化的标志物。用于临床诊断的可行标志物必须能在血液、痰液、支气管肺泡灌洗甚至呼出气冷凝物等“远程介质”中检测到。我们讨论了在这些介质中检测标志物的进展以及迄今为止所识别的分子标志物组合的敏感性和特异性。最后，我们展望了通过对表观基因组的研究可能实现的未来进展。
