Vaid Mudit, Floros Joanna
The Penn State Center for Host-defense, Inflammation and Lung Disease (CHILD) Research, Department of Pediatrics, Penn State Hershey College of Medicine, Hershey, PA 17033, USA.
Oncol Rep. 2009 Jan;21(1):3-11.
Lung cancer is a major cause of cancer-related mortality in both men and women. A 5-year survival of lung cancer patients is only 15% with a negative correlation between progressively advanced lung cancer stage and a 5-year survival period. The only chance for cure is surgical resection if done at the early stage of the disease. Therefore, an early diagnosis and a better prediction of prognosis could decrease mortality. An early diagnosis could provide the opportunity for a therapeutic intervention early in the course of the disease. Genetic alterations in the cancer genome include aneuploidy, deletions and amplifications of chromosomal regions, loss of heterozygosity (LOH), microsatellite alterations, point mutations and aberrant promoter methylation. Of the various types of genetic alterations (i.e. gene amplifications, allele deletions, point mutations or deletions and methylation) reported in different tumor types, aberrant promoter methylation of genes is recent and is the focus of the present review. Specifically, we will briefly review the role of promoter methylation in various malignancies and then focus on lung cancer diagnosis and promoter gene methylation with emphasis on the methylation status of genes of the innate host defense, namely the surfactant proteins A and D.
肺癌是男性和女性癌症相关死亡的主要原因。肺癌患者的5年生存率仅为15%,且肺癌分期越晚,5年生存期越短,二者呈负相关。如果在疾病早期进行手术切除,是治愈的唯一机会。因此,早期诊断和更好地预测预后可以降低死亡率。早期诊断可以在疾病进程早期提供治疗干预的机会。癌症基因组中的基因改变包括非整倍体、染色体区域的缺失和扩增、杂合性缺失(LOH)、微卫星改变、点突变和异常的启动子甲基化。在不同肿瘤类型中报道的各种基因改变类型(即基因扩增、等位基因缺失、点突变或缺失以及甲基化)中,基因的异常启动子甲基化是最近才出现的,也是本综述的重点。具体而言,我们将简要回顾启动子甲基化在各种恶性肿瘤中的作用,然后重点关注肺癌诊断和启动子基因甲基化,特别强调天然宿主防御基因,即表面活性蛋白A和D的甲基化状态。