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Fig. 3 | Genome Medicine

Fig. 3

From: Hepatocellular carcinoma patients with high circulating cytotoxic T cells and intra-tumoral immune signature benefit from pembrolizumab: results from a single-arm phase 2 trial

Fig. 3

Gene expression profiles in association with response to pembrolizumab. A A volcano plot showing the differentially expressed genes (DEGs) between responders and non-responders. Red and green dots indicate the up-regulated genes in responders (adjusted p-value < 0.05 and log2 fold change > 1) and the up-regulated genes in non-responders (adjusted p-value < 0.05 and log2 fold change < − 1). The X-axis represents the log2-fold changes in expression levels, and the Y-axis represents the statistical significances (-log10-adjusted p-value) between responders and non-responders. Each dot represents one gene. B, C A barplot illustrating the top 20 significantly overlapped MSigDB gene sets (FDR < 0.05) with the DEGs generated in A. Hypoxia was associated with up-regulated genes in responders (B), and liver/HCC-associated genesets were overlapped with up-regulated genes in non-responders (C). Red bar represents statistical significances (-log10 scale) and black dot indicates the proportion of overlapped genes in genesets. D, E GSEA plots representing PID_CD8_TCR_DOWNSTREAM pathway (FDR = 0.0028, NES = 1.81) (D) and KEGG_T_CELL_RECEPTOR_SIGNALING pathway (FDR = 0.012, NES = 1.69) (E) were significantly enriched in responders (PR). F ssGSEA scores of gene markers for neutrophil were up-regulated in non-responders (SD/PD) (Wilcoxon rank-sum p value = 0.093). DEG, differentially expressed gene; FDR, false discovery rate; GSEA, geneset enrichment analysis; NES, normalized enrichment score; PR, partial response; SD, stable disease; PD, progressive disease

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