Advanced Lung Cancer Screening: An Individualized Molecular Nanotechnology Approach.

摘要

This grant utilizes complimentary approaches to improve the early detection of lung cancer, with each aim having independent goals and thus separate utility. Our goal is to explore whether detection of DNA methylation changes and enhanced CT evaluations will add to the specificity of lung cancer detection. In the first year of this proposal, we developed an improved panel of genes hypermethylated in lung cancer, with extraordinarily high specificity and sensitivity. These novel genes were used to develop sensitivity methylation specific PCR assays suitable for biologic fluid testing (sputum and plasma). We also optimized the processing of biologic samples to accomplish improved retention of DNA suitable for methylation detection. In the past year, we have combined this improved method with the newly developed PCR detection and begun to examine biologic fluids from patients with and without lung cancer. For plasma studies, we have examined 141 Cancer patients with plasma and 44 non-cancer patients. For sputum studies, we have examined 89 cancer patients for whom we collected sputum and 23 non-cancer patients with sputum (all with benign pulmonary nodules). Initial studies demonstrate the ability to detect differences in the presence of DNA methylation in cancers compared to controls. Will complete the analysis with an additional 72 Cancer positive and 32 non cancer subjects in the remainder of our funded work. In addition, we have utilized CT data sets of subjects with and without lung cancer to optimize CT as a potential screening tool beyond simply looking for lung nodules. We have data that suggests that parenchymal HU variability may be a potential marker of lung cancer. In combination with these molecular detection approaches, the parenchymal CT imaging approaches should lead to improved screening methods.