Molecular Subtyping of Lung Cancer in Smokers and Never-Smokers: A Subset of Adenocarcinomas Characterized by ASCL1 Expression
CM Ida, MC Aubry, P Yang, F Kosari, G Vasmatzis. Mayo Clinic, Rochester, MN
Background: Gene expression profiling represents a powerful tool to unravel tumor molecular heterogeneity underlying different clinical outcomes of tumors with similar histology and clinical stage, especially amongst non-small-cell lung cancer subtypes. Smoking is a well-established risk factor implicated in lung carcinogenesis. Different tumor molecular pathways seem to be operating in smokers (S) and never-smokers (NS). We performed gene expression profiling to differentiate molecular subtypes in lung cancers.
Design: Frozen lung tumor tissue samples from S and NS were used.
|Lung cancer subtype/ Smoking status||SMOKERS (n=209)||NEVER-SMOKERS (n=261)|
|SQUAMOUS CELL CARCINOMA||25||3|
|SMALL CELL LUNG CARCINOMA||14||-|
|LARGE CELL CARCINOMA||10||5|
Clinical staging and follow-up information was obtained for all patients. Gene expression datasets were generated using microarray technology. For S and NS, unsupervised analysis using a group of differentiation genes assessed molecular clustering and histopathological classification correlation, and Kaplan-Meier curves were generated to evaluate survival.
Results: In S (A) and NS (B), tumors clustered in groups that recapitulate histopathological classification.
Amongst adenocarcinoma (AD), ASCL1, a lung neuroendocrine (NE) differentiation gene, was expressed by a subset of AD (ASCL1+AD). ASCL1+AD was present in 25% of AD in S and 4% of AD in NS,(p=0.0012). Preliminary survival analysis indicates less favorable outcome for ASCL1+AD, particularly in stage I disease (C).
Conclusions: We confirmed gene expression profiling as a robust ancillary method to subtype lung cancer molecularly in both S and NS. We showed that a subset of AD express the NE-related gene ASCL1. These were more frequent among S and were associated with less favorable outcome in stage I disease.
Category: Pan-genomic/Pan-proteomic Approaches to Diseases
Monday, March 22, 2010 1:00 PM
Poster Session II # 218, Monday Afternoon