Development of DNA Methylation Markers for Early Detection of Lung Cancer

开发用于肺癌早期检测的 DNA 甲基化标记

• 批准号: 7149741
• 负责人: ITE A OFFRINGA
• 金额: $ 29.26万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7149741
• 关键词: DNA methylation; clinical research; early diagnosis; lung; neoplasm /cancer

DESCRIPTION (provided by applicant): In the United States, lung cancer is the leading cause of cancer death in men and women of all ethnic groups. This disease, which is mainly caused by smoking, will kill over 160,000 Americans in 2005. In 2002/2003 it was estimated that 20-25% of men and women and almost 22% of high school students smoke. Survival of lung cancer patients is very poor, largely because the disease is difficult to detect at an early stage, when it could still be cured by surgery. Advanced imaging techniques such as spiral computed tomography allow high resolution examination of the lung, but lesions that do not progress to lung cancer are very frequently observed in longtime heavy smokers. Molecular markers that could be detected in the bodily fluids of early stage lung cancer patients would be a very powerful and complementary addition to imaging techniques, that would allow the identification of true lung cancer patients from among those with suspicious lesions. DNA hypermethylation is a modification of DNA that does not change its sequence, but that alters the ability of genes to be expressed. Abnormally increased methylation is frequently observed in cancer, where it causes the silencing of genes that normally keep cell growth and cell survival in check. To date, a number of genes showing increased methylation have been identified, but many of these genes are not methylated in a high enough percentage of lung cancers to be useful as markers. Using a high-throughput system developed at USC, the Laird-Offringa laboratory has recently identified a number of very strong candidate markers that are hypermethylated in lung cancer. This proposal is aimed at validating these markers in all major types of non-small cell lung cancer using 300 archival lung specimens and 300 matched control non-tumor lung (from the same patients), as well as 100 non-lung cancers that metastasized to the lung. Lung specimens from all major ethnic groups (white, black, Hispanic/Latino and Asian/Pacific Islander) will be examined. The ability of these markers to detect lung cancer through the analysis of patient bodily fluids will be determined using a new quantitative technique to examine the plasma, sputum and/or bronchioalveloar wash of 300 lung cancer patients treated at University Hospital, Morris Cancer Center, and Los Angeles County Hospital. The development of sensitive and specific molecular markers for lung cancer is the key to early detection of this disease, and could greatly increase lung cancer patient survival.

描述（由申请人提供）：在美国，肺癌是所有种族的男性和女性癌症死亡的主要原因。这种主要由吸烟引起的疾病将在 2005 年导致超过 160,000 名美国人死亡。2002/2003 年估计有 20-25% 的男性和女性以及近 22% 的高中生吸烟。肺癌患者的生存率非常低，很大程度上是因为这种疾病很难在早期发现，但仍可以通过手术治愈。螺旋计算机断层扫描等先进成像技术可以对肺部进行高分辨率检查，但在长期重度吸烟者中经常观察到未进展为肺癌的病变。可以在早期肺癌患者的体液中检测到的分子标记将是成像技术的一个非常强大和补充的补充，这将允许从那些可疑病变的患者中识别出真正的肺癌患者。 DNA 高甲基化是 DNA 的一种修饰，不会改变其序列，但会改变基因表达的能力。在癌症中经常观察到异常增加的甲基化，它会导致通常控制细胞生长和细胞存活的基因沉默。迄今为止，已鉴定出许多显示甲基化增加的基因，但其中许多基因在肺癌中甲基化的比例不够高，无法用作标记。 Laird-Offringa 实验室利用南加州大学开发的高通量系统，最近鉴定出了许多在肺癌中高度甲基化的非常强的候选标记物。该提案旨在使用 300 个存档肺样本和 300 个匹配对照非肿瘤肺（来自同一患者）以及 100 个转移至非小细胞肺癌的所有主要类型的非小细胞肺癌中验证这些标志物。肺。来自所有主要种族群体（白人、黑人、西班牙裔/拉丁裔和亚洲人/太平洋岛民）的肺标本都将接受检查。这些标记物通过分析患者体液来检测肺癌的能力将通过使用一种新的定量技术来检查在大学医院莫里斯癌症中心治疗的 300 名肺癌患者的血浆、痰和/或支气管肺泡洗液来确定。洛杉矶县医院。开发针对肺癌的敏感且特异的分子标记物是早期发现该疾病的关键，并且可以大大提高肺癌患者的生存率。