| A Cautionary Note on the Evaluation of Biomarkers of Subtypes of a Single Disease (2008) | |||||||||||||
Abstract | |||||||||||||
| Heterogeneity in the molecular characteristics of a disease presents a challenge to investigators attempting to identify biomarkers of the disease. Preceding the biomarker discovery effort with stratification within a heterogeneous disease group, which amounts to grouping disease cases into more homogeneous subtypes, seems to be a natural strategy for discovering subtype-specific biomarkers. This is because biologically more homogeneous subgroups are presumably easier to distinguish from the nondiseased than the entire heterogeneous disease group. The misleading benefits of this two-step approach are illustrated using an example from a protein biomarker discovery project for breast cancer. A potential analytical pitfall in this framework is explained using a conditional probability argument. | |||||||||||||
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