Researchers at Mayo Clinic recently found that a specific pair of proteins may be a successful prognostic biomarker for identifying smoking-related lung cancers.
The clinical significance of neuroendocrine (NE) differentiation in lung adenocarcinoma (AD), and the most appropriate biomarkers for this assessment, has long been debated. In the absence of a gold standard, investigators have most commonly used immunohistochemical (IHC) staining of one or a combination of NE markers, such as chromogranin (CHGA), synaptophysin (SYP), neuron-specific enolase or neural cell adhesion molecule (CD56/NCAM) to assess the role of NE differentiation in lung cancer survival. Notably, previous reports have not included ASCL1, despite the pivotal role this gene has in the development of NE cells in the lung.
"This is exciting because we've found what we believe to be a 'drugable target' here," says George Vasmatzis, Ph.D., a Mayo Clinic molecular medicine researcher and senior author on the study. "It's a clear biomarker for aggressive adenocarcinomas. These are the fast-growing cancer cells found in smokers' lungs."
This study examines the role of ASCL1 in the NE differentiation of lung adenocarcinoma (AD). We find expression of the RET oncogene to be highly associated with expression of ASCL1, and expression of both ASCL1 and RET identifies a subgroup of AD with aggressive behavior and poor patient outcome. ShRNA in vitro experiments support an important link between ASCL1 and RET in pulmonary AD and suggest that ASCL1 may influence the motility of AD cells.
Read the full Article at Oncogene.