Disease-specific and glucocorticoid-responsive serum biomarkers for Duchenne Muscular Dystrophy

Figures

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  Figure 1. Pie chart depicting the biological process and molecular function of serum protein biomarkers identified in GC-naïve DMD (n = 18) compared to healthy controls (n = 12). The elevated proteins (108 in total) were mostly of muscle origin followed by some pro-inflammatory and cell adhesion proteins while the decreased proteins (70 in total) consisted mostly of cell adhesion and cell differentiation factors and some metabolism associated and innate immunity-associated proteins.

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  Figure 2. Pie chart showing the numbers of overlapping and non-overlapping serum protein biomarkers between our study and the most recent study3 that used the same SomaScan approach but on a different DMD and control cohort.

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  Figure 3. Longitudinal trajectory of selected examples of DMD serum protein biomarkers and their association with age. CK-M remained relatively stable over time in young GC-naïve DMD patients (p = 0.506) and in controls (p = 0.622) within the age range studied. Myosin-binding protein C declined over time in DMD (p = 0.0477) and remained unchanged over time in controls. Gelsolin neared significance in its association with age (p = 0.0598); it decreased over time in untreated DMD patients while slightly increasing with age in controls. Alanine aminotransferase-1 while elevated in DMD relative to control remained stable over time in both DMD (p = 0.607) and controls. Green lines are DMD patients (n = 12) and black lines are healthy controls (n = 5). The dashed line represent the regression line in each group. P values are adjusted for multiple testing.

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  Figure 4. Pie chart depicting the biological process and molecular function of pharmacodynamic biomarkers that were increased (21 total) and those that were decreased (86 total) in DMD patients after treatment with GC.

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  Figure 5. Representative exemplar of serum proteins that are not associated with DMD but responded to GC treatment. Left panel shows examples for Ly-9 and MMP3 in cross-sectional analysis using healthy controls (CT, n= 12), GC-naïve DMD patients (DMD, n = 18) and GC treated DMD patients (DMD + GC, n = 31). Right panel shows these same biomarkers in pre and post GC treated DMD patients (n = 10) using paired t-test. P values were adjusted for multiple testing in both cross-sectional and longitudinal analysis (***p < 0.001, **p = 0.016).

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  Figure 6. Representative exemplar of DMD associated biomarkers that responded to GC treatment. Left column shows cross-sectional comparison of the biomarker concentrations in healthy (CT) controls (n = 12), GC-naïve DMD (n = 18), GG treated DMD (n = 31), p values are adjusted for multiple testing. Right panel shows paired t-test analysis of the same biomarker in pre and post GC treated DMD patients (n = 10). (A,B) Lumican was elevated in GC-naïve DMD patients then decreased following GC treatment (****p < 0.001, ***p < 0.02). (C,D) Osteomodulin was slightly lower in GC-naïve DMD patients relative to controls and further decreased following GC treatment (**p = 0.015, *p < 0.05).