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

摘要 这项提案的目标是由MD安德森癌症中心的多学科团队提出的 德克萨斯大学西南癌症中心和匹兹堡大学癌症中心 是探索基于循环蛋白标记物和自身抗体的方法来开发 用血液标记物评估小细胞肺癌的风险 (SCLC)。目前有几个已建立的SCLC蛋白质标记，它们各自缺乏 有足够的性能进行早期检测。此外，申请者小组还发现 通过对小鼠模型和人类的综合分析，获得了几个候选蛋白质标记 小细胞肺癌样本。评估已建立和新发现的候选标记的潜力 为了产生指示窝藏或发展小细胞肺癌风险的标记的组合面板， 验证研究将使用最多5年前收集的血浆样本进行 小细胞肺癌的诊断，来自欧洲大型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，在诊断小细胞肺癌时收集的血浆和治疗后以及 将询问组织分子图谱，以确定与候选人的生物学相关性 致SCLC。将实施两种方法来识别抗原蛋白质和肽，这些蛋白质和肽 诱导可挖掘的自身抗体用于小细胞肺癌的早期检测。由Ig界组成的一个 小细胞肺癌患者血浆中的蛋白质和另一种新的方法包括询问 全基因组衍生多肽阵列与等量小细胞肺癌血浆的反应性 循环蛋白质的验证。由此产生的最有希望的标记组合将 使用诊断前的小细胞肺癌样本和来自美国的匹配对照进一步验证 前列腺癌、肺结肠癌和卵巢癌(PLCO)队列。申请者小组有一条坚实的路线 与项目目标相关的协作和专业知识记录，并具有严格的实验经验 设计用于肺癌生物标志物的发现和验证研究。

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.