Array-based outcome prediction in head and neck cancer

描述（由申请人提供）：头颈部鳞状细胞癌（HNSCC）是全球第五大常见恶性肿瘤，代表了一个主要的国际健康问题。这些肿瘤构成了一组解剖学上异质的肿瘤，来自不同的解剖位置，包括口腔，口咽，下咽，喉和鼻咽。HNSCC的治疗计划在很大程度上取决于疾病的解剖分期。手术和/或放疗和/或化疗的常规治疗与影响言语、吞咽和总体生活质量的显著发病率相关。尽管采取了这些干预措施，但仍有约50%的患者在局部、区域或远处复发，相关死亡率很高。有一些确定的分子标志物，可以可靠地用于HNSCC的早期检测或作为预后的指标。因此，迫切需要鉴定可在初始诊断时用于预测患者预后的预后分子标志物，以便在开始时可使用更适当的治疗以改善结果。这个高度合作的研究项目的目标是通过测量100个独立肿瘤样本中至少20，000个不同基因的转录丰度变化来确定预测肿瘤行为和患者预后的特定分子事件。该项目的具体目标是：1）检验HNSCC临床标本中的全局基因表达模式包含可用作预后预测因子的信息的假设。我们将使用含有28，000个cDNA克隆的人cDNA微阵列对一组100个HNSCC患者肿瘤样品应用cDNA表达阵列分析和比较基因组杂交（CGH）阵列分析。2）来自这些实验的组合数据将用作“学习集”以鉴定与组织病理学、转移、这些患者的临床结果和存活率3）我们将使用免疫组织化学技术和市售抗体，使用病理学系和Montefiore医学中心构建的HNSCC组织阵列，

DESCRIPTION (provided by applicant): Head and neck squamous cell carcinoma (HNSCC) is the fifth most common malignancy worldwide, representing a major international health problem. These tumors constitute an anatomically heterogenous group of neoplasms, arising from diverse anatomic locations including the oral cavity, oropharynx, hypopharynx, larynx and nasopharynx. Treatment planning for HNSCC depends largely on anatomical staging of the disease at presentation. Conventional treatment with surgery and/or radiation therapy, and/or chemotherapy is associated with significant morbidity affecting speech, swallowing and overall quality of life. Despite these interventions, recurrence of the disease is observed in about 50% of patients, locally, regionally or at a distant site with high rates of associated mortality. There have been few identified molecular markers that can be reliably used in early detection of HNSCC or as indicators of prognosis. There is therefore an urgent need to identify prognostic molecular markers that can be used at the time of initial diagnosis to predict patient prognosis so that more appropriate treatments can be used at the outset to improve outcome. The goal of this highly collaborative research project is to identify the specific molecular events that predict tumor behavior and patient outcome in this disease by measuring variation in transcript abundance for at least 20,000 different genes in one hundred independent tumor samples. The specific aims of the project are: 1) To test the hypothesis that the pattern of global gene expression in a HNSCC clinical specimen contains information that can be used as a predictor of prognosis. We will apply cDNA expression array analysis and comparative genome hybridization (CGH) array analysis to a set of 100 HNSCC patient tumor samples using a human cDNA microarray containing 28,000 cDNA clones, 2) Combined data from these experiments will be used as a "learning set" to identify gene expression changes and genome copy number aberrations that correlate with histopathology, metastasis, clinical outcome and survival in these patients 3) We will assess the quantity and cellular distribution of the products of identified prognostic genes using immunohistochemical techniques with commercially available antibodies using a HNSCC tissue array constructed in the Department of Pathology and Montefiore Medical Center