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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

基本信息

批准号：
8464024
负责人：
Guy Richard Adami
金额：
$ 7.5万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
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：
2012-05-01 至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8464024
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 Gene Expression Profiling 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

项目摘要

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

描述（由申请人提供）：鳞状细胞癌（SCC）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。尽管目前治疗取得了进展，但口腔鳞状细胞癌 (OSCC) 的生存率仍然很低，主要原因是原发肿瘤在诊断后 3-5 年内复发。晚期肿瘤或具有侵袭性的肿瘤复发得更早。已经测试了肿瘤的各种临床和病理参数，例如侵袭性生长和分化状态，以确定它们预测肿瘤侵袭性的能力。淋巴结转移至多个淋巴结或扩散至淋巴结被膜外，是具有高复发风险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。最近的工作强调使用来自手术获得的原发性肿瘤组织的 RNA 进行全局基因表达分析，识别与淋巴结转移相关的基因表达模式，从而识别高风险肿瘤。我们希望扩展这种方法，以利用可以通过细胞学刷非侵入性获得的细胞，而无需使用手术刀活检。我们之前发表了这种方法，并在仓鼠和人类中鉴定了 2 个 OSCC 特异性标记物：β 2 微球蛋白 (B2M) 和细胞色素 p450 1B1 (CYP1B1)。我们继续使用刷细胞学中的 RNA 确定了 OSCC 的试点基因表达分类器，准确度为 91%。虽然刷细胞学检查细胞形态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方式对恶性病变进行预后。在为期两年的研究中，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种临床/病理指标，这些指标在不易扩散的侵袭性较小的肿瘤中很少发现。我们将使用相同的患者基因表达数据来创建一个基于基因表达的试验分类器，该分类器可以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

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Gene expression based evidence of innate immune response activation in the epithelium with oral lichen planus.

DOI：
10.1016/j.archoralbio.2013.12.010
发表时间：
2014-03
期刊：
Archives of oral biology
影响因子：
3
作者：
Adami GR;Yeung AC;Stucki G;Kolokythas A;Sroussi HY;Cabay RJ;Kuzin I;Schwartz JL
通讯作者：
Schwartz JL

A loss of profilin-1 in late-stage oral squamous cell carcinoma.