LACE-Bio-II: Identification, validation and implementation of prognostic and/or p

描述(申请人提供)：来自四个关键的非小细胞肺癌佐剂试验(IALT，CALGB 9633，JBR.10，ANITA)的研究人员组成了肺佐剂顺铂评估(LACE)-Bio-I联盟，对每个小组在收集的福尔马林固定肿瘤(FFPE)上确定的生物标记物进行交叉验证/汇集荟萃分析，以确认它们在更大的数据集中的稳健性/实用性。Lace-Bio-I主要关注免疫组织化学方法(IHC)和单基因分析。JBR.10还收集了部分患者的新鲜冷冻肿瘤(FFT)和正常肺组织，并发现了一个对预后有很强预测作用的mRNA表达特征，并可能预测从顺铂/长春瑞滨ACT中受益。随着肺癌基因组测序工作的进行，以及代表NSCLC关键致癌驱动因素的新基因异常的发现，我们也迫切需要一种更具适应性的策略来探索这些新标记作为早期患者预后和预测标记的价值。Lace-Bio-II有了新的战略方向。我们将探索基于核酸的新标记，包括基因拷贝数变化(扩增和缺失)、体细胞基因突变，以及可能涉及多基因mRNA签名的基于RNA的标记。利用Lace-Bio FFPE肿瘤样本，我们计划验证JBR.10 15基因预后和预测性信使核糖核酸信号，评估已知潜在癌基因突变的预后和预测值，并探索基因复制变异的预后和预测值。我们还将在冷冻的JBR.10样本上鉴定和评估通过下一代测序发现的新的基因组异常的预后和预测价值。使用从FFPE样本中提取的核酸材料来分析和量化基因组像差的新的高性能和灵敏的技术已经被开发出来，并被引入临床实验室改进修正案(CLIA)批准的实验室。如果我们的策略成功，识别和验证的标记物可以迅速引入临床实践。

DESCRIPTION (provided by applicant): Investigators from the four pivotal adjuvant NSCLC trials (IALT, CALGB 9633, JBR.10, ANITA) formed the Lung Adjuvant Cisplatin Evaluation (LACE)-Bio-I consortium to conduct cross-validation/pooled meta-analyses of biomarkers that each group had identified on collected formalin fixed tumor (FFPE) to confirm their robustness/utility in a larger dataset. LACE-Bio-I had a focus predominantly on immunohistochemical methods (IHC) and single gene analyses. JBR.10 also collected fresh frozen tumor (FFT) and normal lung in a subset of patients and has identified an mRNA expression signature that is strongly prognostic and may be predictive of benefit from cisplatin/vinorelbine ACT. With the ongoing cancer genome sequencing efforts in lung cancer and the reporting of identification of novel genetic aberrations that represent crucial "oncogenic drivers" in NSCLC, we also urgently need a more adaptive strategy to explore the value of these new markers as prognostic and predictive markers in early stage patients. LACE-Bio-II has a new strategic direction. We will explore novel markers that are nucleic acid based, including gene copy number changes (amplifications and deletions), somatic gene mutations, and RNA-based markers that may involve multi-gene mRNA signatures. Using LACE-Bio FFPE tumor samples, we plan to validate the JBR.10 15-gene prognostic and predictive mRNA signature, evaluate the prognostic and predictive values of known potential oncogenic mutations, and explore the prognostic and predictive values of gene copy variations. We will also identify and evaluate the prognostic and predictive value of novel genomic aberrations discovered by Next Generation Sequencing on snap-frozen JBR.10 samples. New high performance and sensitive technologies for assaying and quantifying genomic aberrations using nucleic acid materials derived from FFPE samples have been developed and been introduced into Clinical Laboratory Improvement Amendments (CLIA)-approved laboratories. Should our strategy be successful, identified and validated markers can be rapidly introduced into clinical practice.