Individualized outcome prediction classifiers were successfully constructed through expression profiling of a total of 8,644 genes in 50 non-small cell lung cancer (NSCLC) cases, which had been consecutively operated on within a defined short period of time and followed up more than five years. The resultant classifier of NSCLCs yielded 82% accuracy for forecasting survival or death five years after surgery of a given patient. In addition, since two major histologic classes may differ in terms of outcome-related expression signatures, histologic type-specific outcome classifiers were also constructed. The resultant highly predictive classifiers, designed specifically for non-squamous cell carcinomas, showed a prediction accuracy of more than 90% independent of disease stage. In addition to the presence of heterogeneities in adenocarcinomas, our unsupervised hierarchical clustering analysis revealed for the first time the existence of clinicopathologically relevant subclasses of squamous cell carcinomas with marked differences in their invasive growth and prognosis. This finding clearly suggests that NSCLCs comprise distinct subclasses with considerable heterogeneities even within one histologic type. Overall, these findings should advance not only our understanding of the biology of lung cancer but also our ability to individualize post-operative therapies based on the predicted outcome. Keywords: cell type comparison and prognosis prediction
Overall design
In the study presented here, a consecutively operated, well-defined cohort of 50 NSCLC cases, followed up more than five years, was used to acquire expression profiles of a total of 8,644 unique genes, leading to the successful construction of supervised learning method-based individualized outcome prediction classifiers with high accuracy. In addition, the identification by means of unsupervised hierarchical clustering analysis of two distinct subclasses of squamous cell carcinomas with interesting histologic distinctions and a significant difference in their prognosis is also reported.
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