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）是一种癌症，遭受了包括胃肠道和气道粘膜在内的部位，是迄今为止口腔癌的主要形式。尽管目前在治疗方面取得了进步，但口服SCC（OSCC）的生存仍然很差，这主要是由于诊断后3 - 5年内重复出现了原发性肿瘤。先进的舞台肿瘤或具有侵略性性质的肿瘤更早地复发。肿瘤的各种临床和病理参数，例如侵入性生长和分化状态，以预测肿瘤侵袭性的能力。淋巴结转移到多个节点，或在节点胶囊外传播，是重复发生高风险的攻击性肿瘤的关键指标，但检测这些因素并不总是准确或容易的任务。最近的工作强调了从手术获得的原发性肿瘤组织中使用RNA，以允许全球基因表达分析，以鉴定与淋巴结转移相关的基因表达模式 - 从而鉴定出高风险肿瘤。我们想扩展这种方法，以利用细胞可以通过细胞刷无创，而无需使用手术刀活检。我们以前发表了此方法，并在仓鼠和人类中确定了2个特定标记，β2微球蛋白（B2M）和细胞色素P450 1B1（CYP1B1）。我们继续使用Brush细胞学中的RNA确定OSCC的试验基因表达分类器，精度为91％。虽然对刷细胞学细胞的细胞形态检查已经证明有助于肿瘤检测，但对这些细胞的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，该平台将使临床医生以非侵袭性方式对恶性病变进行预后。在一项为期两年研究的时间范围内，我们建议开发可测试的基于口腔细胞学的基因表达分类器，该分类器将通过多个淋巴结转移，囊外扩散，周期性侵袭和/或差的分化来区分肿瘤 - 四个攻击性的四个临床/病理指标在侵略性较小的肿瘤中很少发现的肿瘤生长，而肿瘤较少易于扩散。我们将使用相同的患者基因表达数据来创建基于试验基因表达的分类器，该分类器直接预测治疗后第一年复发并导致死亡率的肿瘤。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检验的无创方法，以区分最具侵略性的口服癌症与那些不易转移的癌症。尽管许多临床和组织学参数已被用来预测肿瘤复发，但很难将其标准化以进行广泛使用。最接受的标记物高水平淋巴结转移需要颈部手术才能获得最大的精度，这是一种具有高长期发病率的手术。需要一种非侵入性方法来尽早确定哪种治疗方法最适合单个口腔肿瘤。我们将开始测试用刷子收集的肿瘤细胞的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。