Method for Identifying and Monitoring Lung Cancer Patients Using Gene Expression in Blood Cells
Researchers at The Wistar Institute have identified a group of genes in peripheral blood cells that are biomarkers of early stage lung cancer, which can be used to develop a screening, diagnostic, or monitoring assay for lung cancer. While early detection and early treatment of cancer produce the best outcomes, today there is no routine screening test for lung cancer in patients at high risk for the disease. The available screening modalities for smokers and others at high risk for lung cancer (e.g. bronchoscopy, sputum cytology, chest x-ray or low-dose CT scans) are either expensive and or have a high false positive rate. As a result, 50% of new lung cancers are diagnosed at Stage IIIb or IV and the mortality rate of this disease has not improved over the last 30 years.
Peripheral blood samples can provide an easily accessible and affordable means for screening and monitoring individuals at risk for developing lung cancer. Wistar researchers have identified and characterized gene expression patterns in peripheral blood cells that show strong associations with the presence of early stage (Stage 1A and 1B) lung cancers. These researchers have identified gene expression patterns that can distinguish patients with early stage lung cancer from individuals with smoking related inflammatory lung disease or chronic obstructive pulmonary disease (COPD). These gene patterns can be readily analyzed in a blood sample and can identify patients with lung cancer with an accuracy of 87% using just 15 genes. Such a test can be used to screen smokers and others at high risk for lung cancer since the assay does not require a lung biopsy. Surgical removal of the lung cancer reduces or eliminates the cancer gene expression pattern in the peripheral blood so expression of the same set of genes can be used to monitor patients for tumor recurrence following treatment.
Method for Diagnosing and Staging Cutaneous T-Cell Lymphoma Using Gene Expression in Blood Cells
Cutaneous T-cell lymphoma (CTCL) is a form of non-Hodgkin's lymphoma that affects the skin and involves malignant T-lymphocytes. There are about 20,000 patients with CTCL in North America and about 14,000 patients in Europe. The disease usually occurs in middle-aged adults and develops over an extended period of time. CTCL is difficult to diagnose, especially in its early stages, since the symptoms closely resemble those of more common skin ailments. If correctly diagnosed and treated early, CTCL patients can expect to survive for many years. However, the survival rate decreases as the disease progresses to more advanced stages. As a result, a major need exists for methods that can provide reliable early-stage diagnosis of CTCL.
To address this need, scientists at Wistar have identified gene expression profiles using complementary DNA (cDNA) microarray technology that can help in the diagnosis of patients with CTCL. By combining quantitative PCR (qPCR) and linear discriminant analysis, the scientists have adapted the cDNA microarray method and developed a reliable and practical diagnostic for CTCL using as few as 5 genes.
Additionally, expression patterns of a small number of genes (less than 10) can be predictive of patients that will undergo rapid advancement of the disease. Using this technology, gene expression patterns in samples from patients with Sezary Syndrome, an aggressive form of CTCL, were distinguishable from those in patients with more indolent stages of the disease. These changes may contribute significantly to the development and progression of CTCL and provide markers for the use of more aggressive forms of therapy than may otherwise be recommended.