Figure 4.
Olink serum soluble analyte assessment. A, Heat map of dynamic changes in protein expression. The x-axis shows the protein names, while the y-axis shows the comparisons between timepoints and progression. The color represents the logFC. Green represents increase from baseline while pink represents decrease. The size of the circle indicates the statistical significance expressed as –log10(FDR). B, Boxplots and median rend lines showing the expression over time by cohort for CXCL9 and CXCL13. C, Heat map for differential protein expression between responders and nonresponders. The x-axis shows the protein names, while the y-axis shows each timepoint. The symbol in the heat map represents the statistical significance: circles for FDR < 0.05 or adjusted P values, squares for P < 0.05, and triangles for nonsignificant or P > 0.05. The color represents the change relative to upregulation in responders (blue) or nonresponders (red). D, Boxplots corresponding to significant markers in C over time, stratified by treatment arm for the indicated proteins. Comparisons for individual baseline, cycle 2, and cycle 4 timepoints are shown for P < 0.05 and FDR < 0.05 with (*) and (**), respectively. E, Heat map showing the concordance in directionally of differentially expressed proteins significant between exceptional responders and all responders. The direction of the protein changes was identical between both groups of responders, but only CXCL13 and CCL23 reached statistical significance (FDR, darker colors) for exceptional responders due the decreased numbers. Nominal significance is shown as transparent colors, indicating proteins with P < 0.05. F, Volcano plot showing the proteins significantly associated with OS when jointly modeling cytokine expression over time. The proteins labeled in blue are associated with increased HR or decreased survival. Kaplan–Meier OS curves for CSF-1, IL8, CXCL13, and MMP12 stratified on the basis of their expression from the average expression (higher values from the mean as blue, lower values from the mean as red).