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: 7683844
• 负责人: ITE A OFFRINGA
• 金额: $ 28.86万
• 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/7683844
• 关键词: Adenocarcinoma; American; Area; Asians; Biological Markers; Blood; Bronchoalveolar Lavage; Cancer Center; Cancer Etiology; Cancer Patient; Cancer cell line; Cancerous; Carcinogens; Cell Survival; Cessation of life; Clinical; Collection; County Hospitals; CpG Islands; DNA; DNA Methylation; DNA Modification Process; Detection; Development; Disease; Early Diagnosis; Ensure; Environmental Exposure; Ethnic group; Exposure to; Gastrointestinal tract structure; Gene Silencing; Genes; Hispanics; Histologic; Hypermethylation; Imaging Techniques; Individual; Laboratories; Latino; Lead; Lesion; Liquid substance; Los Angeles; Lung; Lung Neoplasms; Malignant Neoplasms; Malignant Squamous Cell Neoplasm; Malignant neoplasm of lung; Metastatic Neoplasm to the Lung; Methylation; Neoplasm Metastasis; Non-Small-Cell Lung Carcinoma; Operative Surgical Procedures; Pacific Island Americans; Patients; Plasma; Polymerase Chain Reaction; Procedures; ROC Curve; Recruitment Activity; Research Personnel; Resolution; Sampling; Sensitivity and Specificity; Series; Smoke; Smoker; Smoking; Specificity; Specimen; Spiral Computed Tomography; Sputum; Staging; Structure of parenchyma of lung; Students; System; Techniques; Testing; Time; Tissues; Tumor Tissue; Tumor-Suppressor Gene Inactivation; United States; University Hospitals; Woman; advanced disease; base; cancer cell; candidate marker; case control; cell growth; emotional distress; high risk; high school; high throughput screening; killings; lung cancer screening; men; molecular marker; programs; promoter; racial and ethnic; repository; sample collection; tumor

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.

在美国，肺癌是所有种族男性和女性癌症死亡的主要原因 组。这种主要由吸烟引起的疾病将在 2005 年夺去 16 万美国人的生命。 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早期发现 阶段，仍可通过手术治愈。先进的成像技术，例如螺旋计算 断层扫描可以对肺部进行高分辨率检查，但未进展为肺癌的病变 在长期重度吸烟者中很常见。可在体内检测到的分子标记 早期肺癌患者的体液将是成像的一个非常强大和补充的补充 技术，这将能够从可疑的肺癌患者中识别出真正的肺癌患者 病变。 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，一个 已经鉴定出许多显示甲基化增加的基因，但其中许多基因并未被识别。 在足够高比例的肺癌中甲基化，可用作标记物。使用高通量 南加州大学开发的系统，莱尔德-奥夫林加实验室最近发现了一些非常强大的系统 肺癌中高甲基化的候选标记物。该提案旨在验证这些 使用 300 个存档肺样本和 300 个匹配的非小细胞肺癌所有主要类型的标记物 对照非肿瘤性肺癌（来自同一患者），以及 100 种转移至肺部的非肺癌 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/太平洋岛民）的肺标本 将接受检查。这些标记物能够通过分析患者的身体来检测肺癌 将使用新的定量技术来检查血浆、痰和/或 对在莫里斯癌症中心大学医院接受治疗的 300 名肺癌患者进行支气管肺泡冲洗，以及 洛杉矶县医院。肺癌敏感、特异分子标志物的开发 是早期发现这种疾病的关键，并且可以大大提高肺癌患者的生存率。