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. 2019 Jan 31;38(21):4047–4060. doi: 10.1038/s41388-019-0700-2

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — In silico analyses of the Ital-Mex TNBC cohort and GSE21653 stratified according to PD-L1 expression. a KEGG analysis of the gene pathways differentially expressed in PD-L1^High and PD-L1^Low TNBC cases (tumors divided by median, n = 158). Bar plot shows significantly enriched gene pathways upregulated in PD-L1^High Ital-Mex TNBC cases versus PD-L1^Low. The bar plot shows the significant top enrichment scores (−log p value). b GSEA enrichment plots of Jak-stat signaling, T cell receptor signaling, and negative regulation of WNT gene sets in PD-L1^High compared with PD-L1^Low TNBC cases. The enrichment score (ES) describes the degree to which a gene set is overrepresented in the ranked list of genes. The NES computes the density of modified genes by the number of genes annotated in each gene cluster, allowing comparisons between conditions. In every panel, the green curve represents the running ES for the gene set as the analysis moves down in the ranked list. The maximum peak is the final ES computed for the gene set (peak score). The middle portion of the plot (lines representation) shows where the gene members of the gene set appear in the ranked list and the expression status described by the color heat-map (red, over-expressed; blue, down-modulated). The leading-edge subset, which represents the gene members that contributed most to the ES, is shown as follows: for a positive ES, the leading edge appears to the left of the maximum peak (left side of the plot), and for a negative ES, the leading edge appears subsequent to the peak score (right side of the plot). c Upper panel: boxplot showing the distribution of SS in PD-L1^High and PD-L1^Low TNBC cases (cutoff median) of the Ital-Mex cohort, and c lower panel: GSE21653 validation cohort (n = 84). d Scatter plot of PD-L1 expression levels evaluated by IHC (y-axis) and mRNA array (x-axis) in 63 matched TNBC cases stratified as SS^High/PD-L1^High (n = 19), SS^High/PD-L1^Low (n = 20), SS^Low/PD-L1^High (n = 6), SS^Low/PD-L1^Low (n = 18). e Scatter plot of PD-L1 expression levels (z-score, x-axis) and stemness score (z-score, y-axis) in ITAL-MEX TNBC cases sub-classified for SS^High/PD-L1^High (n = 36) or f for SS^Low/PD-L1^Low (n = 40). The correlation status was calculated by a Pearson correlation and the p-value for each of the two tumor groups