A cautionary note on the evaluation of biomarkers of subtypes of a single disease.
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.
Adewale
Adeniyi J
AJ
Merck Research Laboratories, North Wales, PA, USA.
Liu
Qi
Q
Dinu
Irina
I
Lampe
Paul D
PD
Mitchell
Bree L
BL
Yasui
Yutaka
Y
D014408:Biomarkers, Tumor / Q000097:blood* / Q000145:classification*; D001943:Breast Neoplasms / Q000097:blood* / Q000145:classification; D015331:Cohort Studies; D006801:Humans; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D014408:Biomarkers, Tumor