Fig. 1. Validation analysis of the cetuximab sensitivity (CTX-S) signature score in two independent sets of CRC patient samples derived from clinical trials and one set of in vitro cetuximab-treated CRC cell lines.

A. A waterfall plot of objective response (OR) vs. adjusted CTX-S score in MK0646 PN004 wild-type (WT) KRAS CRCs (n=44) (see Supplementary Table S1 for detailed data description). The p value is for Barnard’s exact test (OR: No OR) (see Supplementary Table S10A). B. Kaplan Meier (KM) survival (PFS) analysis by higher (>0) vs. lower (<0) CTX-S scores was also performed the PN004 CRCs (n=41). Note: for A, B, of 44 CRCs, one sample with PFS of 1 day and two samples with CTX-S scores near 0.00 as shown in Fig. 1A were excluded from Barnard test and KM analysis. Also see Supplementary Fig. S3 for similar KM analysis on OS. C. KM survival (PFS) analysis by the CTX-S quartile scores was performed in Khambata-Ford et al. (2007) cetuximab-treated CRCs (n=80)(4). D. KM PFS analysis in Khambata-Ford WT KRAS patients (n=43). Also see Supplementary Table S10B,C for the Cochran-Mantel-Haenszel test showing the significant association of the CTX-S score with improved response (CR/PR and SD). E. Spearman correlation analysis of the CTX-S score with in vitro growth inhibition (%) by 10 μg/ml of cetuximab in Medico et al. (2015) cetuximab treated CRC cell lines (20). The analysis was performed in all cell lines (n=147) and WT RAS (KRAS/NRAS) cell lines (n=77) as well as MSS (n=87) and MSI cell lines (n=60), respectively (see detailed data description in Supplementary Table S3A). Note that the results for the other doses of cetuximab (1, 25, 50 and 100μg/ml) were similar, as 10 μg/ml had a 0.945 or higher (Pearson) correlation with these doses for in vitro growth inhibition (Supplementary Table S3B).