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. 2017 Jan;19(1):147–161. doi: 10.1016/j.jmoldx.2016.09.007

Figure 2.

Figure 2

Validation of individual genes and development/evaluation of multigene signatures in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort. A: The REMARK diagram; 1508 estrogen receptor–positive (ER+) METABRIC samples were used for FGFR1 amplification analyses. B: Disease-specific survival (DSS) Kaplan-Meier (KM) curves of true FGFR1 amplification status, as determined by single-nucleotide polymorphism (SNP) array copy number analysis stratified by ER status, demonstrated that FGFR1 amplification is prognostic in ER+ tumors but not in ER- tumors. In parentheses are total number of events/total number of samples with valid survival and FGFR1 amplification data. The hazard ratios (HRs) with associated 95% CIs and the log-rank test P values (P) are reported. C: Individual receiver operating characteristic (ROC) curve confirms the discriminative ability of each individual gene for FGFR1 amplification. The solid black point indicates the optimal cutoff point on each ROC curve. The legend shows area under the ROC curve (AUC), sensitivity, and specificity corresponding to the optimal cutoff. D: Overlaid KM curves for DSS indicate that each of the four composite signatures is prognostic and tracks the true nonamplified curve well. KM curves of amplification statuses, as determined by each of the four multigene signatures from 10-fold cross-validations (red dashed curves: upper/lower red curves for nonamplified/amplified patients, respectively), were overlaid by gold standard FGFR1 amplification status, as determined by SNP array copy number analysis (black solid curves, upper/lower curves for nonamplified/amplified patients, respectively), and amplification status, as determined by both a signature and the true status (green dotted curves, upper/lower curve for nonamplified cases determined by both/amplified cases determined by both, respectively). The HRs with associated 95% CIs and the log-rank test P values (P) are reported. The signature Call-FGFR1-amp based on the optimal AUC (optAUC) algorithm was carried forward locked down for validation. EMP, empirical method; Logistic, logistic regression method; NB, naïve Bayes method.