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

LACE-Bio-II：预后和/或 p 的识别、验证和实施

• 批准号: 8680036
• 负责人: LESLEY Katie SEYMOUR
• 金额: $ 43.12万
• 依托单位: QUEEN'S UNIVERSITY AT KINGSTON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-14 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8680036
• 关键词: Adjuvant; Adjuvant Chemotherapy; Amendment; Biological Assay; Biological Markers; Cancer and Leukemia Group B; Cisplatin; Clinical; Collaborations; DNA; Data Set; Evaluation; Formalin; Freezing; Gene Dosage; Gene Expression Profile; Gene Mutation; Genes; Genetic; Genomics; Goals; Laboratories; Lung; Malignant neoplasm of lung; Messenger RNA; Meta-Analysis; Methods; Molecular Profiling; Mutation; Non-Small-Cell Lung Carcinoma; Nucleic Acids; Oncogenic; Operative Surgical Procedures; Patients; Performance; Predictive Value; Prognostic Marker; RNA; Reporting; Research Personnel; Resectable; Sampling; Staging; Technology; Testing; Tissues; Toxicity due to chemotherapy; Validation; Variant; Vinorelbine; base; cancer genome; clinical practice; cohort; experience; genome sequencing; mRNA Expression; next generation sequencing; novel; novel marker; prognostic; tumor; validation studies

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.

描述（由申请人提供）：来自四项关键辅助 NSCLC 试验（IALT、CALGB 9633、JBR.10、ANITA）的研究人员组成了肺辅助顺铂评估 (LACE)-Bio-I 联盟，对各组在收集的福尔马林固定肿瘤 (FFPE) 上鉴定的生物标志物进行交叉验证/汇总荟萃分析 以在更大的数据集中确认它们的稳健性/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 还收集了一部分患者的新鲜冷冻肿瘤 (FFT) 和正常肺，并确定了具有强烈预后意义的 mRNA 表达特征，并且可以预测顺铂/长春瑞滨 ACT 的益处。随着肺癌癌症基因组测序工作的持续进行以及代表非小细胞肺癌关键“致癌驱动因素”的新型遗传畸变的鉴定报告，我们还迫切需要一种更具适应性的策略来探索这些新标记物作为早期患者预后和预测标记物的价值。 LACE-Bio-II有了新的战略方向。我们将探索基于核酸的新型标记，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 特征的基于 RNA 的标记。我们计划使用 LACE-Bio FFPE 肿瘤样本验证 JBR.10 15 基因预后和预测 mRNA 特征，评估已知潜在致癌突变的预后和预测价值，并探索基因拷贝变异的预后和预测价值。我们还将鉴定和评估下一代测序在速冻 JBR.10 样本上发现的新型基因组畸变的预后和预测价值。使用源自 FFPE 样品的核酸材料测定和量化基因组畸变的新型高性能和灵敏技术已经开发出来，并已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。