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。在腺癌患者中，最近针对肺癌患者进行了基于突变的治疗发展，并且迫切需要改善鳞状细胞癌患者（SCC）的治疗，这是美国每年67,000例新患者的亚型。此外，SCC正在吸烟，因为SCC患者主要是当前或以前的吸烟者，并且被严重污名化为患有“自我造成的疾病”。 SCC的研究严重资金不足（可能是出于同样的原因）。该提案利用一种多机构和多学科的方法来验证SCC预后的先前基因表达特征，目的是将这些特征带入更广泛的临床适用测定法（即RT-QPCR）。但是，我们还希望确定针对SCC患者治疗的新靶标。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，以预后SCC的预后。我们将使用来自至少3年随访的临床注释人群收集的300个SCC肿瘤，并在一个标准化的实验室平台中验证mRNA和miRNA签名。在此目标中，我们将将这些签名转换为基于RT-QPCR的测定法。在AIM 2中，我们将验证2个独立合作组临床试验队列中最强大的签名；一个来自Calgb（n = 150分），另一个来自AcoSog（n = 250分）。这些研究的终点是预后（与疾病有关的生存）。在AIM 3中，我们将利用上述生物测量资源开始验证NCI的癌症基因组鉴定的基因组变异，并评估它们的流行率，以及它们是否可以补充目标1和2中定义的标志的签名能力。虚拟SCC组织库与分子，病理和临床信息有关。