Squamous Cell Carcinoma of the Lung: Validation of Molecular Signatures for Progn

肺鳞状细胞癌：预后分子特征的验证

基本信息

批准号：
8690549
负责人：
FRED R HIRSCH
金额：
$ 58.07万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-09 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8690549
关键词：
Academic Medical Centers Accounting Adenocarcinoma Adjuvant Adjuvant Therapy Affect American College of Surgeons Oncology Group Atlases Biological Assay Biological Markers Cancer Etiology Cancer and Leukemia Group B Cessation of life Clinic Clinical Clinical Trials Cooperative Group Colorado DNA Sequence Data Data Analyses Data Set Databases Disease Evaluation Exons Formalin Freezing Frequencies Future Gene Expression Gene Expression Profile Genes Genomics Goals Histopathology Hospitals In Situ Hybridization Individual Institution Laboratories Lead Link Location Lung Lung Adenocarcinoma Malignant Neoplasms Malignant neoplasm of lung Messenger RNA Methods Michigan MicroRNAs Modeling Molecular Molecular Profiling Morbidity - disease rate Mutation Non-Small-Cell Lung Carcinoma Nucleotides Oncogenic Operative Surgical Procedures Outcome Paraffin Embedding Pathway interactions Patients Performance Population Prevalence Property Quantitative Reverse Transcriptase PCR RNA Recurrence Relapse Reporting Reproducibility Research Research Personnel Resected Resources Risk Sampling Silver Smoker Smoking Specimen Squamous Cell Lung Carcinoma Squamous cell carcinoma Staging Systemic Therapy Testing The Cancer Genome Atlas Therapeutic Tissue Banking Tissue Banks Triage Universities Validation Variant Washington Woman base cancer genome cancer genomics candidate selection clinical practice clinically significant cohort demographics experience follow-up high risk improved interdisciplinary approach men molecular marker mortality nano-string novel novel therapeutics outcome forecast prognostic statistical center therapeutic development tumor virtual

项目摘要

DESCRIPTION (provided by applicant): Lung cancer is the most common cause of worldwide cancer deaths. Recent mutation based therapeutic developments for patients with lung cancer have occurred in those with adenocarcinomas, and there is an urgent need for improved management of patients with squamous cell carcinoma (SCC), a subtype accounting for 67,000 new patients per year in the US. Furthermore, SCC is smoking related as SCC patients are mostly current or former smokers and severely stigmatized as having a "self-inflicted disease". Research in SCC is severely underfunded (possibly for this same reason). This proposal leverages a multi-institutional and multidisciplinary approach to validate preexisting gene expression signatures for prognosis of SCC, with the goal to bring these signatures to a more broadly clinical applicable assay (i.e. RT-qPCR). However, we also hope to identify new targets for therapy for patients with SCC. The proposal has 3 aims. In Aim1 we will validate previously defined gene array (mRNA) and miRNA expression signatures for prognosis in early stage SCC. We will use 300 SCC tumors collected by different institutions from clinically annotated cohorts with at least 3 years follow-up, and validate mRNA and miRNA signatures in one standardized laboratory per assay platform. In this aim, we will transform these signatures into RT-qPCR based assays. In Aim 2 we will validate the most robust signatures in 2 independent cooperative group clinical trial cohorts; one from CALGB (N=150 pts.) and one from ACOSOG (N=250 pts.). The endpoint of these studies is prognosis (disease related survival). In Aim 3, we will leverage the biospecimen resources described above to begin validation of genomic variants being identified by NCI's Cancer Genome Atlas Project and assess their prevalence and whether they can supplement the prognostic power of the signatures defined in Aims 1 and 2. We have established a Squamous Lung Cancer Consortium (SLCC) of experienced clinical and biomarker investigators and we will establish a central SCC database including a virtual SCC tissue bank linked to molecular, pathological, and clinical information.

描述（由申请人提供）：肺癌是全球癌症死亡的最常见原因。最近针对肺癌患者的基于突变的治疗开发已出现在腺癌患者中，并且迫切需要改进对鳞状细胞癌 (SCC) 患者的治疗，鳞状细胞癌 (SCC) 是美国每年新增患者 67,000 名的亚型。此外，鳞状细胞癌与吸烟有关，因为鳞状细胞癌患者大多是当前或以前的吸烟者，并被严重污蔑为患有“自残性疾病”。 SCC 的研究资金严重不足（可能出于同样的原因）。该提案利用多机构和多学科方法来验证预先存在的 SCC 预后基因表达特征，目标是将这些特征应用于更广泛的临床适用检测（即 RT-qPCR）。然而，我们也希望为鳞状细胞癌患者找到新的治疗靶点。该提案有 3 个目标。在 Aim1 中，我们将验证先前定义的基因阵列 (mRNA) 和 miRNA 表达特征，以预测早期 SCC 的预后。我们将使用不同机构从临床注释队列中收集的 300 个 SCC 肿瘤，并进行至少 3 年的随访，并在每个检测平台的一个标准化实验室中验证 mRNA 和 miRNA 特征。为此，我们将把这些特征转化为基于 RT-qPCR 的检测方法。在目标 2 中，我们将验证 2 个独立合作组临床试验队列中最稳健的特征；一份来自 CALGB（N=150 分），一份来自 ACOSOG（N=250 分）。这些研究的终点是预后（疾病相关生存）。在目标 3 中，我们将利用上述生物样本资源开始验证 NCI 癌症基因组图谱项目鉴定的基因组变异，并评估其患病率以及它们是否可以补充目标 1 和 2 中定义的特征的预后能力。建立了由经验丰富的临床和生物标志物研究人员组成的鳞状肺癌联盟 (SLCC)，我们将建立一个中央 SCC 数据库，包括与分子、病理和临床相关的虚拟 SCC 组织库信息。