This study demonstrated that there is an optimal level of CD44 that correlates with fastest cell migration in an induced mouse model for glioblastoma. We found that at intermediate CD44 level cells migrated fastest and that mice die most rapidly. If the level of CD44 is either increased or decreased, then migration drops and survival is extended. When we examined published human transcript data, we found the same trend with respect to human high grade glioma survival, even though there was no linear correlation. Thus, our results illustrate the functional relationship between cell migration and survival, and more generally point toward biomarkers being treated as non-monotonic predictors such that survival depends biphasically upon expression level, i.e. there is an optimal level of gene expression leads to poorest outcomes.
Biphasic Dependence of Glioma Survival and Cell Migration on CD44 Expression Level (2017)
[2] Klank, R.L., Decker Grunke, S.A., Bangasser, B.L., Forster, C.L., Price, M.A., Odde, T.J., SantaCruz, K.S., Rosenfeld, S.S., Canoll, P., Turley, E.A., McCarthy, J.B., Ohlfest, J.R., and D.J. Odde (2017). Biphasic Dependence of Glioma Survival and Cell Migration on CD44 Expression Level. Cell Reports, 18, 23-31.