Fig. 1: RNase1 predicts poor prognosis for HCC and poor clinical response of it to anti-PD-1 therapy. | Nature Communications

Fig. 1: RNase1 predicts poor prognosis for HCC and poor clinical response of it to anti-PD-1 therapy.

From: Targeting ALK averts ribonuclease 1-induced immunosuppression and enhances antitumor immunity in hepatocellular carcinoma

Fig. 1

a Experimental strategy. Figure was created with BioRender.com. b The 10 most frequently enriched biological process GO terms in nivolumab non-responders. Upregulated genes are functionally annotated using GO terminology using the R-package clusterProfiler. c Volcano plot of fold differences in genes between HCC samples from nivolumab responders (n = 5) and non-responders (n = 5). P values were calculated using the Wald test. Secreted protein-coding genes belonging to the RNase superfamily or known to be associated with human cancer are shown in different colors. d Heat map of the expression of the most differentially expressed secreted proteins in (c) (P < 0.001; 34 upregulated and 10 downregulated genes). Data were analyzed using two-sided t-test. e OS and recurrence probability in HCC patients based on RNase1 expression. f Expression of secreted RNase1 protein in murine and human HCC cells. Representative results from 3 independent experiments. g Enzyme-linked immunosorbent assay (ELISA) analysis of RNase1 expression in plasma samples from HCC patients (n = 67) and normal individuals (n = 15). h Correlation analysis of the plasma RNase1 concentrations and RNase1 expression levels in paired human HCC samples (n = 55; R = 0.6 [two-sided Pearson’s chi-square test]). i OS and recurrence probability in HCC patients based on RNase1 plasma level. j IHC and IF staining of HCC samples from nivolumab responders (n = 5) and non-responders (n = 8). Left: Fluorescent multiplex immunohistochemical labeling using the indicated antibodies upon nivolumab-based treatment (upper panel) and immunohistochemical staining for RNase1 in human HCC samples (bottom panel). Scale bars, 50 μm (inset, 25 μm). Right: RNase1 immunohistochemistry scores for human HCC samples upon nivolumab exposure (n = 13; P = 0.0216). Results are presented as mean ± SD values. Statistical analysis: g two-sided Unpaired Student’s t-test; e and i Log-rank test. Source data are provided as a Source Data file.

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