RNA from Brush Cytology to Identify Aggressive Squamous Cell Carcinoma

刷细胞学 RNA 鉴定侵袭性鳞状细胞癌

• 批准号: 8304010
• 负责人: Guy Richard Adami
• 金额: $ 7.97万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8304010
• 关键词: Address; Aftercare; Biopsy; Brush Cell; Cells; Cellular Morphology; Cervix Neoplasms; Cervix Uteri; Classification; Clinic; Clinical; Cytochrome P450; Cytology; DNA; Data; Dentistry; Detection; Development; Diagnosis; Diagnostic Neoplasm Staging; Distant; Evaluation; Extracapsular; Future; Gene Expression; Gene Expression Profile; Genes; Goals; Growth; Hamsters; Heterogeneity; Human; Hybridization Array; Individual; Lesion; Lymph Node Involvement; Malignant - descriptor; Malignant Neoplasms; Medicine; Metastatic Neoplasm to Lymph Nodes; Methods; Microscopy; Monitor; Morbidity - disease rate; Mouth Neoplasms; Mucous Membrane; Nature; Neck; Neoplasm Metastasis; Non-Malignant; Operative Surgical Procedures; Oral; Oral Pathology; Oral Surgical Procedures; Otolaryngology; Patients; Primary Neoplasm; Procedures; Publishing; RNA; RNA analysis; Recurrence; Risk; Sampling; Site; Squamous cell carcinoma; Testing; Time; Tissues; Tongue; Tumor Tissue; Tumor stage; Variant; Work; base; beta-2 Microglobulin; capsule; college; follow-up; gastrointestinal; high risk; lymph nodes; malignant mouth neoplasm; mortality; mouth squamous cell carcinoma; neoplastic cell; novel strategies; oncology; oral surgery specialty; outcome forecast; perineural; scalpel; standard care; tumor; tumor growth

DESCRIPTION (provided by applicant): Squamous cell carcinoma (SCC), a cancer which afflicts sites including the gastrointestinal and airway mucosa, is by far the predominant form of oral cancer. Despite current advances in treatment, survival from oral SCC (OSCC) remains poor, chiefly due to recurrence of the primary tumor within 3-5 years after diagnosis. Advanced stage tumors, or those of aggressive nature, recur much earlier. Various clinical and pathological parameters of the tumor, such as invasive growth, and state of differentiation have been tested for their ability to predict tumor aggressiveness. Lymph node metastasis to multiple nodes, or spread outside the node capsule, are key indicators of aggressive tumors at high risk for recurrence but detection of these factors is not always accurate or an easy task. Recent work has highlighted the usage of RNA from surgically obtained primary tumor tissue to allow global gene expression analysis that identifies gene expression patterns associated with lymph node metastasis - thus identifying high risk tumors. We would like to extend this approach to take advantage of cells that can be obtained noninvasively with a cytology brush without the use a of scalpel biopsy. We previously published this method and have identified 2 specific markers for OSCC, in hamsters and humans, beta 2 microglobulin (B2M) and cytochrome p450 1B1 (CYP1B1). We have gone on to identify a pilot gene expression classifier for OSCC using RNA from brush cytology with an accuracy of 91%. While examination of cell morphology from brush cytology cells has already proven helpful in tumor detection, RNA analysis of these cells has the potential to contribute to true diagnosis and prognosis. Our long term goal is to develop a platform that will allow the clinician to develop a prognosis for malignant lesions in a noninvasiv manner. In the time frame of a two year study, we propose to develop a testable oral cytology based gene expression classifier that will differentiate tumors with multiple lymph node metastasis, extracapsular spread, perineural invasion and/or poor differentiation- four clinical/pathological indicators of aggressive tumor growth that are seldom found in less aggressive tumors that are less prone to spread. We will use the same patient gene expression data to create a pilot gene expression based classifier that directly predicts tumors that recur and cause mortality the first year after treatment. These gene expression based classifiers will ultimately aid in treatment decisions. 1 PUBLIC HEALTH RELEVANCE: These results will deliver a testable noninvasive method for differentiation of the most aggressive oral cancers from those that are less prone to metastasize. While many clinical and histological parameters have been used to predict tumor recurrence it is difficult to standardize them for widespread usage. The most accepted marker, high level lymph node metastasis, requires neck surgery for greatest accuracy, a procedure with high long-term morbidity. There is a need for a noninvasive method to determine what kind of treatment is best for an individual oral tumor as early as possible. We will begin to test if RNA from tumor cells collected with a brush will be able to yield a gene expression signature that can be used for tumor classification, prognosis and treatment decisions.

描述（由申请人提供）：鳞状细胞癌（SCC）是一种累及胃肠道和气道粘膜等部位的癌症，是迄今为止口腔癌的主要形式。尽管目前的治疗进展，口腔鳞状细胞癌（OSCC）的生存率仍然很低，主要是由于原发性肿瘤在诊断后3-5年内复发。晚期肿瘤或侵袭性肿瘤复发的时间要早得多。已经测试了肿瘤的各种临床和病理学参数，如侵袭性生长和分化状态，以确定其预测肿瘤侵袭性的能力。淋巴结转移到多个淋巴结，或扩散到淋巴结包膜外，是复发风险高的侵袭性肿瘤的关键指标，但这些因素的检测并不总是准确或容易的。最近的工作强调了使用来自手术获得的原发性肿瘤组织的RNA来进行全局基因表达分析，该分析鉴定与淋巴结转移相关的基因表达模式，从而鉴定高风险肿瘤。我们想扩展这种方法，利用细胞，可以获得非侵入性的细胞刷，而不使用手术刀活检。我们以前发表了这种方法，并确定了2个特定的标志物，口腔鳞状细胞癌，在仓鼠和人类，β 2微球蛋白（B2 M）和细胞色素p450 1B 1（CYP 1B 1）。我们已经确定了一个试点的基因表达分类口腔鳞癌使用RNA刷细胞学的准确率为91%。虽然刷状细胞学细胞的细胞形态学检查已被证明有助于肿瘤检测，但这些细胞的RNA分析有可能有助于真正的诊断和预后。我们的长期目标是开发一个平台，使临床医生能够以非侵入性的方式发展恶性病变的预后。在为期两年的研究时间框架内，我们建议开发一种可测试的基于口腔细胞学的基因表达分类器，该分类器将区分具有多个淋巴结转移、囊外扩散、神经周围浸润和/或分化差的肿瘤-侵袭性肿瘤生长的四个临床/病理指标，这在侵袭性较低的肿瘤中很少发现，这些肿瘤不易扩散。我们将使用相同的患者基因表达数据来创建一个基于先导基因表达的分类器，该分类器直接预测治疗后第一年复发并导致死亡的肿瘤。这些基于基因表达的分类器最终将有助于治疗决策。1 公共卫生相关性：这些结果将提供一种可测试的非侵入性方法，用于区分最具侵袭性的口腔癌和不易转移的口腔癌。虽然许多临床和组织学参数已被用于预测肿瘤复发，但很难将其标准化以广泛使用。最被接受的标志物，高水平的淋巴结转移，需要颈部手术的最大准确性，一个高的长期发病率的程序。需要一种非侵入性的方法来尽早确定哪种治疗方法对个体口腔肿瘤最好。我们将开始测试用刷子收集的肿瘤细胞RNA是否能够产生可用于肿瘤分类、预后和治疗决策的基因表达特征。