Bremnes Roy M, Sirera Rafael, Camps Carlos
Department of Oncology, University Hospital of Northern Norway, University of Tromsø, N-9038 Tromsø, Norway.
Lung Cancer. 2005 Jul;49(1):1-12. doi: 10.1016/j.lungcan.2004.12.008.
Lung cancer is the most common cause of cancer death in developed countries. The prognosis is poor with only 10-15% of patients surviving 5 years after diagnosis. This dismal prognosis is attributed to the lack of efficient diagnostic methods for early detection and lack of successful treatment for metastatic disease. Within the last decade, rapid advances in molecular biology and radiology have provided a rational basis for improving early detection and patients' outcome. A non-invasive blood test effective in detecting preneoplastic changes or early lung cancer in high risk individuals has been perceived as a holy grail by cancer researchers.
The introduction of polymerase chain reaction (PCR)-based technology in the late 1980s and its refinement over the last 10 years have allowed us to detect and quantify extremely small amounts of tumour-derived nucleic acids. This has led to an increased knowledge of the molecular pathogenesis of lung cancer and a basis for the use of DNA and RNA markers in blood for early cancer detection, diagnostics, and follow-up. Common genetic alterations in lung carcinogenesis are already well known. We reviewed published literature on DNA and RNA in plasma or serum in lung cancer patients up to 2004, with particular emphasis on reports published since 1995.
Twenty-two clinical studies have evaluating the role of DNA and RNA aberrations in the blood of lung cancer patients. A total of 1618 (range 10-163/study) cases and 595 (range 10-120/study) control cases were evaluated, and overall plasma/serum abnormalities were found in 43% (range 0-78%) of cases and 0.8% of healthy controls. For (1) total DNA and gene expression levels, 61% (range 53-71%) of cases and 0.9% of controls; (2) oncogene mutations, 16% (range 0-30%) and 0%; (3) microsatellite alterations, 46% (range 24-71%) and 21% (controls with non-malignant pulmonary disease); (4) promoter methylation, 42% (range 5-73%) and 0%; (5) tumour-related RNAs, 54% (range 39-78%) and 6%. In general, the studies contain small series of lung cancer patients and even smaller or missing case control groups.
The analysis of circulating DNA or RNA in plasma is a promising non-invasive diagnostic tool, requiring only a limited blood sample. Its wide applicability and potential importance will possibly lead to increasing clinical impact in the near future. However, large prospective clinical studies are needed to validate and standardise any tests for DNA or RNA alteration in plasma or serum of high risk individuals or patients with established lung cancer.
肺癌是发达国家癌症死亡的最常见原因。其预后很差，只有10% - 15%的患者在确诊后能存活5年。这种令人沮丧的预后归因于缺乏有效的早期检测诊断方法以及对转移性疾病缺乏成功的治疗方法。在过去十年中，分子生物学和放射学的快速发展为改善早期检测和患者预后提供了合理依据。一种能有效检测高危个体癌前病变或早期肺癌的非侵入性血液检测被癌症研究人员视为圣杯。
20世纪80年代末基于聚合酶链反应（PCR）技术的引入及其在过去10年的改进，使我们能够检测和定量极少量的肿瘤衍生核酸。这增加了我们对肺癌分子发病机制的认识，并为在血液中使用DNA和RNA标志物进行早期癌症检测、诊断及随访奠定了基础。肺癌发生过程中常见的基因改变已为人熟知。我们回顾了截至2004年关于肺癌患者血浆或血清中DNA和RNA的已发表文献，特别强调了1995年以来发表的报告。
22项临床研究评估了DNA和RNA异常在肺癌患者血液中的作用。共评估了1618例（每项研究范围为10 - 163例）病例和595例（每项研究范围为10 - 120例）对照病例，总体血浆/血清异常在43%（范围为0 - 78%）的病例中被发现，而在健康对照中为0.8%。对于（1）总DNA和基因表达水平，61%（范围为53 - 71%）的病例和0.9%的对照；（2）癌基因突变，16%（范围为0 - 30%）和0%；（3）微卫星改变，46%（范围为24 - 71%）和21%（患有非恶性肺部疾病的对照）；（4）启动子甲基化，42%（范围为5 - 73%）和0%；（5）肿瘤相关RNA，54%（范围为39 - 78%）和6%。总体而言，这些研究纳入的肺癌患者系列较小，病例对照组甚至更小或缺失。
分析血浆中循环DNA或RNA是一种有前景的非侵入性诊断工具，仅需有限的血液样本。其广泛的适用性和潜在的重要性可能会在不久的将来对临床产生越来越大的影响。然而，需要大型前瞻性临床研究来验证和标准化针对高危个体或已确诊肺癌患者血浆或血清中DNA或RNA改变的任何检测。
