Development of Risk and Early Detection Biomarker for Small Cell Lung Cancer

摘要 MD安德森癌症中心的一个多学科小组提出的这项建议的目标是， 德克萨斯大学西南癌症中心和爱丁堡大学癌症中心 是探索基于循环蛋白标记物和自身抗体的方法， 基于血液的标记物面板，以评估小细胞肺癌的风险 （SCLC）。目前存在几种已建立的SCLC蛋白标记物，其单独缺乏 足够的性能用于早期检测。此外，申请人小组还发现， 通过对小鼠模型和人类模型的综合分析， SCLC样品。评估已建立和新发现的候选标记的潜力 为了产生指示具有或发展SCLC的风险的标志物的组合组， 验证研究将使用在研究开始前5年内采集的血浆样本进行。 SCLC的诊断，来自大型欧洲前瞻性调查的参与者， 癌症与营养（EPIC）和新加坡华人健康研究（SCHS）队列。 此外，在SCLC诊断时和治疗后以及 将询问组织分子谱，以确定与候选人的生物学相关性 SCLC。将实施两种方法来鉴定抗原蛋白和肽， 诱导可用于SCLC早期检测的自身抗体。一种由结合的IG组成 SCLC病例血浆中的蛋白质，另一种新方法包括询问 用于与SCLC血浆等分试样反应的全基因组衍生肽阵列， 循环蛋白质的验证。最有希望的标记的组合将 使用来自美国的诊断前SCLC样本和匹配对照进行进一步验证 前列腺、肺、结肠和卵巢（PLCO）队列。申请人群体有实质性的跟踪 与项目目标相关的合作和专业知识记录，实验性 肺癌生物标志物的发现和验证研究的设计。

ABSTRACT The goal of this proposal by a multi-disciplinary team at MD Anderson Cancer Center, the University of Texas Southwestern Cancer Center and the University of Pittsburg Cancer Center is to explore approaches based on circulating protein markers and autoantibodies to develop a blood based marker panel to assess risk of harboring or developing small cell lung cancer (SCLC). There are currently several established SCLC protein markers which individually lack sufficient performance for early detection. Additionally, the applicant group has uncovered several protein marker candidates through integrated analyses of mouse models and human SCLC samples. To assess the potential of established and newly discovered candidate markers to yield a combined panel of markers indicative of risk of harboring or developing SCLC, validation studies will be conducted using plasma samples collected up to 5 years prior to a diagnosis of SCLC, from participants in the large European Prospective Investigation into Cancer and Nutrition (EPIC) and the Singapore Chinese Health Study (SCHS) cohorts. Additonally, plasmas collected at the time of diagnosis of SCLC and post-treatment as well as tissue molecular profiles will be interrogated to establish the biological relevance to candidates to SCLC. Two approaches will be implemented to identify antigenic proteins and peptides that induce autoantibodies that can be mined for SCLC early detection. One consisting of Ig bound proteins in plasmas from SCLC cases and another novel approach consists of interrogating whole genome derived peptide arrays for reactivity with aliquots of SCLC plasmas utilized for validation of circulating proteins. The resulting combination of the most promising markers will be further validated using pre-diagnostic SCLC samples and matched controls from the US Prostate Lung Colon and Ovarian (PLCO) cohort. The applicant group has a substantial track record of collaboration and expertise relevant to project objectives, with rigor in experimental design for discovery and validation studies of lung cancer biomarkers.