Sputum Biomarkers to Detect Lung Carcinogenesis from Field Cancerization
Abstract
This proposal describes a patient-oriented research in the field of lung cancer biomarker discovery. Jun-Chieh James Tsay is an Instructor of Medicine at New York University Division of Pulmonary, Critical Care and Sleep Medicine. He obtained his Master of Science degree in Clinical Investigation Translational Medicine studying genetic expression in the lung. Under the guidance of Dr. William Rom, principal investigator for the National Cancer Institute-funded Early Detection Research Network, he has been involved in lung cancer screening projects and collaborative work developing lung cancer biomarker test. He will be mentored by a committee consisting of experts in biomarker research, RNA genomics, airway epithelial cells, and biostatistics/bioinformatics, who have develop a comprehensive career training plan that focuses on precision medicine through didactic training (molecular oncology and bioinformatics), basic science experiments, and clinical research. Lung cancer is the leading cause of cancer deaths worldwide. It has one of the lowest (15%) 5-year survival rate of all cancers because most patients present with advanced disease. Smoking rates among military personnel are 50% higher than the civilian population while Veteran survival is lower. The National Lung Screening Trial showed a 20% mortality benefit with low-dose CT scan screening, which will help improve detection of early-stage lung cancer. However, a high (96%) false positive rate poses the challenge of avoiding unnecessary procedures to manage indeterminate pulmonary nodules. To improve detection of early-stage lung cancer, there is a need to develop an accurate, affordable, non-invasive test to complement CT screening to reduce the needs for follow-up tests and unnecessary procedures. We hypothesize that epithelial cells in the airway of lung cancer patients express a distinct oncogenic signature, which can be detected in enriched sputum-derived human bronchial epithelial cells and used to develop a highly specific, non-invasive sputum lung cancer biomarker test over the next 2 years. To study the genomic expression in airway epithelial cells and its relationship to lung tumor expression, we propose to perform genetic sequencing of airway brushing epithelial cells in multiple airway segments of lung cancer patients and smoker controls, as well as sequencing lung tumor samples (Aim 1). We hope to use this information to develop candidate lung cancer biomarker that can be detected in enrich sputum-derived human bronchial epithelial cells isolated from induced sputum through advance cell sorting technique (Aim 2). This study is an important step towards understanding the relationship between lung tissue and lung tumor and may reveal information regarding the role lung airway contribute to lung cancer development. We hope the proposed sputum-based cancer biomarker test will help complement CT scan screening to improve lung cancer detection. The long-term goal is to translate this knowledge for personalized medicine by aiding in subtyping lung cancer for optimal treatment, prognosticating individual patient, and discovering novel treatment targets. In this proposal, we considered that while cigarette smoke is the major risk factor of lung cancer development in Veterans, many Veterans were also exposed to other risk factors such as Agent Orange, radon, asbestos, uranium, beryllium, and fuel exhaust. To develop an accurate lung cancer biomarker, research in this field requires recruitment of subject from this group of Veterans. Therefore, we proposed a study that will involve recruitment of Veterans who receive medical care at the New York Manhattan VA hospital. With early detection of lung cancer, we will be able to dramatically decrease the number of lung cancer deaths in our military Veteran population.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610324
Entities
People
- Jun-Chieh Tsay
Organizations
- Grossman School of Medicine
- United States Army