Fig. 1: Longitudinal urine metabolomics identifies diacetylspermine as a metabolic biomarker of doxorubicin effectiveness.

a Experimental design for urine collection of TNBC-PDX TM97 and TM98 mice treated with vehicle (5% dextrose, IV) or doxorubicin (DOXO, 2 mg/kg, IV). b Tumor growth curves showing TM97 resistance and TM98 sensitivity to DOXO treatment. c, d Principal component analysis and loadings plot of untargeted urine metabolomics on day 21. e Venn diagram showing number of significantly altered features with X8.56_287.2451 m.z. being the most significant by two-way repeated measures ANOVA. Tumor refers to the tumor identity (TM97 and TM98) while treatment refers to vehicle or doxorubicin. f Quantified urinary diacetylspermine and g correlation with tumor volume. Data are presented as mean ± s.e.m. or individual values, ***P < 0.001, ****P < 0.0001 vs TM97, ††P < 0.01 vs TM98 control; n = 8–9. Significance was determined by one-way ANOVA with Tukey’s test or two-way repeated measures ANOVA with Sidak’s correction. Correlation plots display 95% confidence intervals. Graphics were generated using Servier Medical Art (smart.servier.com).