Fig. 1

Construction of a four miRNA-based signature. a Hierarchical clustering of 13 serum miRNAs expression level in HER2⁺ MBC. Hierarchical clustering of serum samples from 61 patients responding to treatments (in green) and 42 patients resistant to treatments (in brown) with the 13 differentially expressed miRNAs using Euclidean distance and average linkage clustering. Each row represents an individual miRNA, and each column represents an individual sample. Pseudocolors indicate relative expression levels from low to high on a log2 scale from −3 to 3. P-values are t-tests on the log2-transformed values of the expression data. b Hierarchical clustering shows the collinearity of 13 candidate miRNAs. Correlation matrix heatmap of 13 miRNAs in the training cohort, where each cell represents the Pearson correlation between the row and column corresponding miRNAs. The legend shows the color change along with the change of correlation coefficient from −0.4 to 1.0. c LASSO coefficient profiles of the 13 HER2⁺ MBC-associated serum miRNAs. Each curve corresponds to a miRNA; the vertical line is drawn at the value λ = 0.11 chosen by 200-time cross-validation via 1-SE criteria. d The expression levels of the four miRNAs in serum of 55 healthy volunteer donors, 134 trastuzumab-resistant patients, and 252 trastuzumab-sensitive patients. Error bars in graphs are standard deviation (s.d). *P < 0.05; **P < 0.01; ***P < 0.001. P-values were obtained using two-tailed Student’s t-test