Journal: Advanced Science
Article Title: Proteogenomic Landscape of Breast Ductal Carcinoma Reveals Tumor Progression Characteristics and Therapeutic Targets
doi: 10.1002/advs.202401041
Figure Lengend Snippet: 6q21 Amplification‐Associated NR3C1 Overexpression was Involved in Immune Escape of Tumor Cells in DCIS_Pure. A) Boxplot illustrating the immune scores across different stages of BRDC progression: Normal ( n = 19), DH ( n = 54), DCIS_Pure ( n = 30), DCIS_adjIDC ( n = 43), and IDC ( n = 78). The box represents the interquartile range (IQR) from the first (Q1) to the third quartile (Q3) of the distribution, and the line inside the box represents the median. The whiskers extend from Q1 to Q3 to the endpoints, which are defined as the most extreme data points within Q1 − 1.5 × IQR and Q3 + 1.5 × IQR, respectively. Student's t ‐test, **** p < 0.0001. B) Heatmap illustrating cell type compositions and activities of selected individual genes/proteins and pathways across the BRDC progression stages. The heatmap in the first section illustrated the immune/stromal signatures from xCell. The heatmap in the second section illustrates the protein abundances of sterol hormone receptors and immune‐related marker CD8A. ssGSEA scores based on global proteomic and phosphoproteomic data for biological pathways upregulated in different progression stages of BRDC are illustrated in the remaining sections. ANOVA test, * p < 0.05, *** p < 0.001, **** p < 0.0001. C) Comparison of the protein expression levels of sterol hormone receptors between the DH ( n = 54) and DCIS_Pure ( n = 30). The p value was calculated by Student's t ‐test. D) Volcano plot showing the correlation between the protein expression levels of NR3C1 TFs and their corresponding CNA. The red points show the cis ‐effect TFs (Spearman's rho > 0.2, p < 0.05). Histogram showing the fold changes of the protein expression levels of the cis ‐effect TFs in DCIS_Pure compared with DH. Student's t ‐test (upper left corner). E) Heatmaps showing copy number alteration (CNA) of PRDM1 , the protein abundances of PRDM1 and NR3C1, the immune score, and the pathway score of TNF‐α signaling via NF‐ĸB in DH and DCIS_Pure. Student's t ‐test, * p < 0.05, *** p < 0.001, **** p < 0.0001. F) Boxplot showing the transcriptional activities of NF‐ĸB1 and RelA in DH ( n = 54) and DCIS_Pure ( n = 30). Student's t ‐test, * p < 0.05, **** p < 0.0001. G) Volcano plot showing the correlations between the transcription factor activity of NF‐ĸB1 and RelA and the pathway scores by ssGSEA. The one highlighted in red represents the pathway of cytokine‐cytokine receptor interaction (Spearman's rho = 0.72, p = 1.61e‐14). H) Heatmaps showing the protein expression levels of CXCL12 and CX3CL1 (upper) and the mRNA levels of CXCL12 and CX3CL1 (bottom) in DH and DCIS_Pure. Student's t ‐test, * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001. I) Spearman‐rank correlation of the protein expression levels of CX3CL1 and CD8A. J) Representative IHC images of NR3C1 and CD8 on DH, DCIS_Pure, and DCIS_adjIDC tissues. Scale bars = 50 µm. K) The paradigm of the immune alteration among the DH, DCIS_Pure, and DCIS_adjIDC.
Article Snippet: Mutant TP53: mouse monoclonal anti‐P53 (1:800, Leica Biosystems, Cat# PA0067); ESR1: mouse monoclonal anti‐ESR1 (1:500, Abcam, Cat# ab241557); NR3C1: rabbit monoclonal anti‐NR3C1 (1:1000, Abcam, Cat# ab183127); CD8A: rabbit polyclonal anti‐CD8A (1:50, Invitrogen, Cat# PA5‐11453); TIAM1: rabbit polyclonal anti‐TIAM1 (1:100, Cloud‐clone, Cat# PAC778Hu01); AR: rabbit polyclonal anti‐AR (1:200, Gene Tech, Cat# GT245202); AKR1C1: rabbit polyclonal anti‐AKR1C1 (1:500, GeneTex, Cat# GTX105620).
Techniques: Amplification, Over Expression, Marker, Comparison, Expressing, Activity Assay