Lung cancer surpasses all other causes of cancer-related deaths worldwide. Gene-expression microarrays have shown that differences in the cytologically normal bronchial airway can distinguish between patients with and without lung cancer. In research reported here, we have used microRNA expression in bronchial epithelium and gene expression in nasal epithelium to advance biological understanding of the lung-cancer "field of injury" and develop new biomarkers for lung cancer diagnosis.
MicroRNAs are known to mediate the airway response to tobacco smoke exposure but their role in the lung-cancer-associated field of injury was previously unknown. Microarrays can measure microRNA expression; however, they are probe-based and limited to detecting annotated microRNAs. MicroRNA sequencing, on the other hand, allows the identification of novel microRNAs that may play important biological roles. We have used microRNA sequencing to discover novel microRNAs in the bronchial epithelium. One of the predicted microRNAs, now known as miR-4423, is associated with lung cancer and airway development. This finding demonstrates for the first time a microRNA expression change associated with the lung-cancer field of injury and microRNA mediation of gene expression changes within that field.
The National Lung Screening Trial showed that screening high-risk smokers using CT scans decreases lung-cancer-associated mortality. Nodules were detected in over 20% of participants; however, the overwhelming majority of screening-detected nodules were non-malignant. We therefore need biomarkers to determine which screening-detected nodules are benign and do not require further invasive testing. Given that the lung-cancer-associated field of injury extends to the bronchial epithelium, our group hypothesized that the field of injury may extend farther up in the airway. Using gene expression microarrays, we have identified a nasal epithelium gene-expression signature associated with lung cancer. Using samples from the bronchial epithelium and the nasal epithelium, we have established that there is a common lung-cancer-associated gene-expression signature throughout the airway. In addition, we have developed a nasal epithelium gene-expression biomarker for lung cancer together with a clinico-genomic classifier that includes both clinical factors and gene expression. Our data suggests that gene expression profiling in nasal epithelium might serve as a non-invasive approach for lung cancer diagnosis and screening
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/14145 |
| Date | 22 January 2016 |
| Creators | Gerrein, Joseph |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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