Extended Data Fig. 6: HIF1α and U34 enzymes levels are upregulated in samples from patients with metastatic and drug-resistant melanoma.
From: Codon-specific translation reprogramming promotes resistance to targeted therapy
a, Representative images of indicated proteins detected by immunohistochemistry are shown in human melanoma biopsies classified by Clark index. b, Immunohistochemistry staining of indicated proteins were performed in primary melanoma samples (n = 25) and in metastasis (n = 12). Quantification is shown on the right and representative images are shown on the left. Two-sided t-test, data are mean + s.d. c, Correlation index (Pearson coefficient) of samples in b. d, e, HIF1α signature (d, invasive (INV), n = 95 independent samples; proliferative (PRO), n = 82 independent samples) and U34 enzymes (e, invasive, n = 95 independent samples; proliferative, n = 82 independent samples) are elevated in short-term cultured melanoma lines of the invasive compared to proliferative phenotype (classification from Chapman et al.15). d, Two-tailed Wilcoxon matched-pairs signed-rank test. e, Two-tailed Mann–Whitney U-test. d, e, Data are median, minimum and maximum. f, Schematic representing the selection of samples from patients with BRAFV600E melanoma. g, Elevated MITFlow signature expression is correlated with resistance to BRAF inhibition. BRAFV600E melanoma cell lines (n = 28) from the CCLE cohort were used to correlate PLX4720 (BRAF inhibition) IC50 concentrations with the expression of the MITFlow signature (Pearson correlation coefficient R; statistical test: non-FDR corrected, two-tailed t-test). h, The expression of the U34-enzyme signature (that is, ELP1–ELP3–ALKBH8–CTU1–CTU2) and the HIF1α signature (HIF1A–GLUT1-GLUT3–VEGFA–LDHA–CXCR4–MCT4–PDK1) was evaluated in MITFlow and MITFhigh populations. MITFlow, n = 59 independent samples; MITFhighn = 128 independent samples; two-tailed Mann–Whitney U-test; data are the median and 25th to 75th percentile (see ‘Statistical analysis’).
