Fig. 2: Oncogenic activation of S100A9 in both Brca1-MT mice and human breast cancer patients. | Nature Communications

Fig. 2: Oncogenic activation of S100A9 in both Brca1-MT mice and human breast cancer patients.

From: S100A9-CXCL12 activation in BRCA1-mutant breast cancer promotes an immunosuppressive microenvironment associated with resistance to immunotherapy

Fig. 2

a Workflow of DIA-MS analysis with mammary tissues during tumorigenesis, including mammary gland tissues from 8–10 months Wild type (WTMG) and Brca1-MT (MTMG) virgin mice, tumor- adjacent mammary tissues (Tu-Adj. MG), and tumors from both Wild type (WTBT) and Brca1-MT (MTBT) mice (n = 3 mice/per genotype). b Plot of Principal Component Analysis (PCA) of samples from the same cohort of samples in (a). c Pearson correlation analysis of duplicate of each sample from the same cohort samples in a. d The patterns of increased the protein level of S100A9 during tumorigenesis with the same cohort of samples in a from DIA data analysis with Spectronaut and statistics analysis by Pearson correlation (FDR < 1, r = 0.8343, adjust p value = 0.024. The raw data are transformed by log10,the box and whisker plots summarize the normalized values, line show the SD). The data are from n = 3 biologically independent replicates. e Pearson correlation of BRCA1 and S100A9 at protein level by volcano plot from Clinical Proteomics Tumor Analysis Consortium (CPTAC) for The Cancer Genomic Atlas (TCGA) database (http://www.linkedomics.org/admin.php). f Heatmap of top 50 genes which are negatively correlated with BRCA1 at protein level from e. g Overlapping of mouse candidate gene lists from DIA analysis with top 45 genes which are negatively regulated by BRCA1 genes. h The representative images of S100A9 antibody staining on BRCA1-WT and BRCA1-MT breast cancer tissues (n = 2 in each group from PDX models) were obtained from Jackson Laboratory. i Quantifications of S100A9 positive cells per field in h, (n = 22 pictures from WT and 30 from MT in h models). j Survival outcome based on S100A9 expression of breast cancer patients (n = 4934) from Kaplan–Meier Plotter website (https://kmplot.com/analysis/index.php?p=service&cancer=breast). k, l Relative expression of S100a9 and S100a8 of mammary tissues in 4-months Brca1-WT and MT virgin mice (k) and Brca1 MT and WT mammary tumors (l) revealed by qPCR (n = 3 mice/group) and the number of dots represents biological replicates). m, n Protein levels of S100a9 and S100a8 in 4-month-old mammary tissues (m), and in Brca1 MT and WT tumors (n) as determined by western blots (n = 3 mice/group). The data are expressed as means ± SD (d, i, k, l) and P values determined by unpaired two-tailed Student’s t test (i, k, l). Scale bar: black color, 50 μM. Source data are provided as a Source data file.

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