Peptide-based slides for improving the diagnostic quality of sputum specimens - SUMMARY/ABSTRACT
Lung cancer is the leading cause of cancer-related mortality in both men and women in United States with a
dismal 5-year survival rate of 15%. While surgery is the only curative option, 70% of the patients are diagnosed
with inoperable advanced disease, thus highlighting a lack of effective early screening methods. Typically, low
dose computed tomography (LDCT) is used as the primary screening modality, however, 90-95% of suspicious
lung lesions identified by LDCT eventually are found to be benign. As a result, such patients undergo medically
unnecessary procedures and treatments, resulting in increased cost, time and morbidity. Hence there is an
urgent need to develop a non-invasive complementary screening technique which can identify the high-risk
population for lung cancer and thus enable detection of lung lesions at an early and potentially curable stage. To
this end, cytological and molecular aberrations found in exfoliated bronchial epithelial cells in sputum of smokers
have shown a strong correlation to lung cancer incidence. However, these diagnostically important cells
represent less than 1% of the cellular composition of sputum, thus making their detection extremely challenging.
Hence, it is essential to develop a method which can isolate and capture these scant yet important cells, while
removing the other obscuring cells from sputum and thereby improve the clinical utility of these vital
biospecimens. The goal of this Phase I application is to develop a novel peptide-coated glass slide, which can
selectively capture and retain the epithelial cells of interest in a peptide-modified region, while moving the
obscuring cells to a separate region of the slide. Epithelial cell capture on the peptide-modified slides will be first
optimized to identify lead peptides for subsequent clinical testing. Thereafter compatibility of the peptide-modified
slides with commonly employed clinical staining techniques will be established. Finally, the feasibility of using
these peptide-modified slides for capturing cells from human sputum specimens will be validated. Successful
completion of this project will not only allow for better visualization of the captured epithelial cells to the clinicians,
but also enable further downstream processing of these cells to identify molecular and/or genetic atypia present,
because of the non-destructive nature of this technology.
