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Non-invasive Biomarker Panels for Early Detection of Lung Squamous Cell Carcinoma

用于早期检测肺鳞状细胞癌的非侵入性生物标志物组合

基本信息

批准号：
8505002
负责人：
Feng Jiang
金额：
$ 29.94万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8505002
关键词：
Accounting Achievement Baltimore Basic Science Biological Assay Biological Markers Biometry Body Fluids Bronchoscopy Cancer Center Cancer Etiology Cancer Patient Cessation of life Chronic Obstructive Airway Disease Clinical Complement Cytopathology Data Detection Diagnosis Diagnostic Diagnostic Procedure Early Diagnosis Environment Epithelial Cells Evaluation Functional RNA Future Genetic Variation Genomics Goals Individual Interdisciplinary Study Lung Malignant Neoplasms Malignant Squamous Cell Neoplasm Malignant neoplasm of lung Maryland Measures Medical center Molecular Molecular Genetics Outcome Pathology Patient Care Patients Performance Prevention Pulmonology Research Resources Sampling Screening for cancer Secure Sensitivity and Specificity Small Nucleolar RNA Solid Specimen Sputum Sputum Cytology Screening Squamous Cell Lung Carcinoma Staging Structure of parenchyma of lung Techniques Testing Thoracic Surgical Procedures Tissues Training Translating Translational Research Universities Validation Work Workload X-Ray Computed Tomography base cancer diagnosis case control clinical application clinical practice clinically significant cost effective therapy improved innovation interest mortality oncology outcome forecast respiratory response screening success

项目摘要

DESCRIPTION (provided by applicant): This application is submitted in response to PA-09-199 "Identifying non-coding RNA (ncRNA) targets for cancer early detection and prevention (R01)". Our objective is to develop sputum-based small ncRNA biomarkers that can combine with the genomic probes to improve early detection of lung squamous cell cancer (LSqCC). LSqCC is the second most frequent lung cancer. In 2010, LSqCC will cause an estimated 47,190 deaths, accounting for 8.4 % of all cancer deaths in the USA. Given the poor prognosis associated with advanced stage LSqCC, its early detection will potentially reduce the mortality. However, the current diagnostic techniques for LSqCC early detection are either invasive or have poor accuracy. We have collected induced sputum samples from early stage LSqCC patients and cancer-free controls. We developed an enrichment technique that can efficiently collect deep respiratory epithelial cells from the sputum samples. We also developed sputum-based genomic probes that can diagnose LSqCC with higher sensitivity compared with sputum cytology. However, the sensitivity of the probes is not high enough for clinical application. Small ncRNAs are emerging as potential biomarkers in cancer diagnosis. We have been the first to demonstrate that miRNAs are stably present in sputum. Furthermore, using microarrays to analyze 42 early stage LSqCC tissues and paired noncancerous lung tissues, we recently identified 39 LSqCC-associated small ncRNAs. The ncRNAs include 30 miRNAs and 9 snoRNAs, providing new potential biomarkers for diagnosis of the malignancy. Therefore, we hypothesize that combining the ncRNA biomarkers with the genomic probes in sputum will improve early detection of LSqCC. Taking advantage of our well-characterized induced sputum samples of the cases and controls, we will perform the following four specific aims: 1), determining whether the miRNAs and snoRNAs can be accurately and robustly measured in sputum by qRT-PCR, 2), optimizing a panel of highly specific and sensitive ncRNA biomarkers for early stage LSqCC in a training set of the sputum specimens, 3), validating the ncRNA biomarkers in an testing set of the samples, and 4), evaluating the combined use of the ncRNA biomarkers and genomic probes for early detection of LSqCC. Future application of the biomarkers in clinical settings will potentially provide a useful means to improve early detection of LSqCC, and hence reduce the mortality. The study will strongly support one of the PA's main interests "Combination of ncRNA and genetic variation markers in body fluids to increase accuracy of cancer diagnosis".

描述(申请人提供)：本申请是响应PA-09-199《识别用于癌症早期检测和预防的非编码RNA(NcRNA)靶标(R01)》而提交的。我们的目标是开发基于痰的小ncRNA生物标记物，可以与基因组探针相结合，提高对肺鳞状细胞癌(LSqCC)的早期检测。LSqCC是第二常见的肺癌。2010年，LSqCC估计将导致47,190人死亡，占美国所有癌症死亡人数的8.4%。鉴于晚期LSqCC预后较差，早期发现LSqCC有可能降低死亡率。然而，目前用于LSqCC早期检测的诊断技术要么是侵入性的，要么是准确性差的。我们收集了早期LSqCC患者和无肿瘤对照的诱导痰样本。我们开发了一种浓缩技术，可以有效地从痰标本中收集深部呼吸道上皮细胞。我们还开发了以痰为基础的基因组探针，与痰细胞学相比，它可以更敏感地诊断LSqCC。然而，这些探针的灵敏度还不够高，不适合临床应用。小的ncRNAs正在成为癌症诊断的潜在生物标志物。我们是第一个证明miRNAs稳定存在于痰中的人。此外，使用微阵列分析了42例早期LSqCC组织和配对的非癌肺组织，最近我们发现了39个LSqCC相关的小ncRNAs。NcRNAs包括30个miRNAs和9个snoRNAs，为恶性肿瘤的诊断提供了新的潜在生物标志物。因此，我们推测，将ncRNA生物标志物与痰中的基因组探针相结合将有助于LSqCC的早期发现。利用我们完善的病例和对照诱导痰样本，我们将执行以下四个具体目标：1)确定是否可以通过qRT-PCR准确和可靠地检测痰中的miRNAs和snoRNAs；2)在痰标本的训练集中优化一组高度特异和敏感的ncRNA生物标记物用于早期LSqCC；3)验证样本测试集中的ncRNA生物标记物；以及4)评估ncRNA生物标记物和基因组探针联合用于LSqCC早期检测的效果。未来生物标志物在临床上的应用将有可能为提高LSqCC的早期发现提供有用的手段，从而降低死亡率。这项研究将有力地支持PA的主要兴趣之一，即结合体液中的ncRNA和遗传变异标记，以提高癌症诊断的准确性。