RNA from Brush Cytology to Detect Squamous Cell Carcinoma

利用刷细胞学 RNA 检测鳞状细胞癌

• 批准号: 8123395
• 负责人: Joel L Schwartz
• 金额: $ 16.56万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-09 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8123395
• 关键词: Biopsy; Cancer Model; Cancerous; Carcinoma in Situ; Cell Nucleus; Cells; Clinic; Collecting Cell; Cytology; DNA Microarray Chip; Data; Dental Care; Dentistry; Dentists; Detection; Development; Diagnosis; Disease; Early Diagnosis; Epithelium; Evaluation; Foundations; Future; Gastrointestinal tract structure; Gene Expression; Gene Expression Profile; Genes; Genetic; Hamsters; Histopathology; Hospitals; Human; Human Papillomavirus; Left; Lesion; Leukoplakia; Malignant - descriptor; Malignant Neoplasms; Medicine; Messenger RNA; Methodology; Methods; Microscopic; Modeling; Modification; Mucous Membrane; Non-Malignant; Operative Surgical Procedures; Oral; Oral Surgical Procedures; Oral cavity; Otolaryngology; Patients; Pilot Projects; Premalignant; Procedures; Production; RNA; RNA analysis; Research Personnel; Sampling; Screening for Oral Cancer; Severe dysplasia; Shapes; Site; Solutions; Squamous cell carcinoma; Staging; System; Temperature; Testing; Time; Tissues; Validation; Veterans Hospitals; Work; base; clinical Diagnosis; college; disease diagnosis; follow-up; gastrointestinal; genetic analysis; improved; malignant mouth neoplasm; mouth squamous cell carcinoma; oral lesion; oral premalignancy; oral surgery specialty; outcome forecast; prognostic; prospective; prototype; public health relevance; scalpel; tool; tumor

DESCRIPTION (provided by applicant): Squamous cell carcinoma, a cancer which afflicts sites including the gastrointestinal and airway mucosa, is by far the predominant form of oral cancer. Paradoxically, while oral squamous cell carcinoma, OSCC, typically initiates as visible lesions in the oral cavity, early detection of the disease at this curable stage is limited. This is likely due to the high number of other more innocuous oral lesions that occur that can resemble OSCC, and the necessity for a surgical biopsy for accurate detection and diagnosis of the disease. Brush oral cytology can be used to collect cells from suspect lesions without surgery, which in turn can be used for microscopic analysis of malignant changes but with decreased accuracy. We propose a method of lesion evaluation that uses this same noninvasive procedure, brush cytology, but to provide RNA to allow gene expression analysis of the lesion mucosa. We have shown that this methodology, contrary to preconceived ideas that it would not be feasible, provided high quality RNA capable of allowing the differentiation of OSCC from normal mucosa in a hamster oral cancer model. We will take advantage of recent studies that have shown in surgically biopsied tissue that class predictors, based on changes in global gene expression, can be developed that can accurately diagnose malignant disease. The study proposed will determine if RNA from cytology can be analyzed to produce a global gene expression signature that can be used to detect OSCC. Prospective OSCC patients, prior to undergoing standard biopsy diagnosis for OSCC, will be subjected to brush oral cytology to allow us to develop, and then validate, a gene expression signature that identifies OSCC. An immediate result will be a noninvasive methodology to accurately detect and contribute to the diagnosis of OSCC, ready to be further validated in other clinics. Next, we will apply this same approach to develop a gene expression based class predictor for the earliest stage of squamous cell carcinoma, moderate to severe dysplasia and carcinoma in situ. After analysis of RNA from brush cytology from pre-cancerous oral lesions, we will use statistical methodologies optimized for heterogeneous samples to develop a class predictor for these early malignancies based on gene expression of a small set of genes. In the end, we will start to determine if the detection and diagnosis of oral premalignancies and OSCC using RNA from brush cytology is superior to the OralCDx system. 1 PUBLIC HEALTH RELEVANCE: These results should deliver a noninvasive method for detection of the vast majority of oral cancers that is validated against even the earliest stages of the disease. It will be ready to be tested in additional clinics with other investigators. This should allow the earlier detection of oral cancer and could save lives immediately. This finding would strongly support the usage of the RNA from brush cytology approach with other gastrointestinal and airway passage cancers. This study would also determine the feasibility of noninvasive brush cytology methods to detect oral premalignancies and deliver a prototype predictor. With some modifications, such as the usage of commercially available room temperature RNA stabilization solutions, this would bring us much closer to an economical, noninvasive form of oral cancer screening.

描述（由申请人提供）：鳞状细胞癌是一种影响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。矛盾的是，虽然口腔鳞状细胞癌（OSCC）通常以口腔中可见的病变开始，但在这个可治愈阶段对该疾病的早期发现是有限的。这可能是由于存在大量其他更无害的口腔病变，可能类似于 OSCC，并且需要进行手术活检来准确检测和诊断该疾病。口腔刷细胞学检查可用于在不进行手术的情况下从可疑病变中收集细胞，进而可用于恶性变化的显微分析，但准确性较低。我们提出了一种病变评估方法，该方法使用相同的非侵入性程序（刷细胞学），但提供 RNA 以允许对病变粘膜进行基因表达分析。我们已经证明，与先入为主的想法相反，这种方法是不可行的，它提供了能够在仓鼠口腔癌模型中区分 OSCC 和正常粘膜的高质量 RNA。我们将利用最近的研究，这些研究表明，在手术活检组织中，可以开发基于全局基因表达变化的分类预测因子，从而准确诊断恶性疾病。拟议的研究将确定是否可以分析细胞学中的 RNA 以产生可用于检测 OSCC 的全局基因表达特征。潜在的 OSCC 患者在接受标准的 OSCC 活检诊断之前，将接受刷口腔细胞学检查，以便我们开发并验证识别 OSCC 的基因表达特征。直接的结果将是一种能够准确检测和诊断 OSCC 的非侵入性方法，并准备在其他诊所进行进一步验证。接下来，我们将应用相同的方法来开发基于基因表达的早期鳞状细胞癌、中度至重度不典型增生和原位癌的类别预测因子。在对癌前口腔病变刷细胞学的 RNA 进行分析后，我们将使用针对异质样本优化的统计方法，基于一小组基因的基因表达来开发这些早期恶性肿瘤的类别预测因子。最后，我们将开始确定使用刷细胞学 RNA 检测和诊断口腔癌前病变和 OSCC 是否优于 OralCDx 系统。 1 公共健康相关性：这些结果应该提供一种非侵入性方法来检测绝大多数口腔癌，甚至可以针对疾病的最早阶段进行验证。它将准备好与其他研究人员一起在其他诊所进行测试。这应该可以更早地发现口腔癌，并可以立即挽救生命。这一发现将有力支持将刷细胞学方法中的 RNA 用于其他胃肠道和气道癌症。这项研究还将确定非侵入性刷细胞学方法检测口腔癌前病变并提供原型预测因子的可行性。通过一些修改，例如使用市售的室温 RNA 稳定溶液，这将使我们更接近经济、非侵入性的口腔癌筛查。

项目成果

Analysis of RNA from brush cytology detects changes in B2M, CYP1B1 and KRT17 levels with OSCC in tobacco users.

刷细胞学 RNA 分析可检测烟草使用者 OSCC 中 B2M、CYP1B1 和 KRT17 水平的变化。

• 发表时间: 2011-06
• 影响因子: 4.8
• 作者: Kolokythas, Antonia;Schwartz, Joel L;Pytynia, Kristen B;Panda, Suchismita;Yao, Mike;Homann, Brian;Sroussi, Herve Y;Epstein, Joel B;Gordon, Sara C;Adami, Guy R
• 通讯作者: Adami, Guy R

A prototype tobacco-associated oral squamous cell carcinoma classifier using RNA from brush cytology.

使用来自刷细胞学的 RNA 的原型烟草相关口腔鳞状细胞癌分类器。

• 发表时间: 2013-10
• 作者: Kolokythas, Antonia;Bosman, Mitchell J;Pytynia, Kristen B;Panda, Suchismita;Sroussi, Herve Y;Dai, Yang;Schwartz, Joel L;Adami, Guy R
• 通讯作者: Adami, Guy R