Fig. 3: Impacts of copy number alterations on sunitinib therapeutic outcomes.
From: Proteogenomics of clear cell renal cell carcinoma response to tyrosine kinase inhibitor
a Cox regression analysis of significant arm-level CNA events, based on the PFS. b Comparison of gene-level CNAs between Responders and Non-Responder in this cohort. The upper plot illustrates the frequency of CNA events and the lower plot illustrates the −log10 (p value) of each gene for the comparison of Responders and Non-Responder (two-sided Fisher’s exact test). c Heatmap depicting the protein expression levels positively correlated with the Chromosome 7q copy number. Two-sided Spearman’s correlations are shown in the right panel. The values were transformed by z-score. d Boxplots depicted the expression of LAMTOR4 (proteome level: 7q gain n = 30, non-7q gain n = 55; transcriptome level: 7q gain n = 31, non-7q gain n = 62), MDH2 (proteome level: 7q gain n = 31, non-7q gain n = 62; transcriptome level: 7q gain n = 31, non-7q gain n = 62), and CALU (proteome level: 7q gain n = 31, non-7q gain n = 62; transcriptome level: 7q gain n = 31, non-7q gain n = 62) between 7q gain and non-7q gain cohort at transcriptome and proteome level, separately (two-sided Wilcoxon rank-sum test). The line represents the mean with SEM and upper and lower quartiles, respectively. P values were described in the figure. e Overexpression of LAMTOR4, MDH2, and CALU increased the phosphorylation of S6K. Numerical values below the gels indicate quantification of the bands relative to control. f The immunohistochemical (IHC) for pS6K in the tumor and tumor-adjacent tissue of responders and non-responders (analyzed patients: n = 3). The scale bar indicates 80 μm. g CCK-8 detected the effect of LAMTOR4, MDH2, and CALU overexpression and Sunitinib treatment on cell proliferation. (Sunitinib-200 nM, n = 9 independent experiments, two-sided t-test). Data were presented as mean values ± SD. P values were described in the figure. ns not significant. h Proposed model explaining the 7q gain-induced Sunitinib treatment non-response. Source data are provided as a Source Data file.
