Clinical significance of upregulated Rho GTPase activating protein 12 causing resistance to tyrosine kinase inhibitors in hepatocellular carcinoma

Figure 1 Research overflow of this study. ARHGAP12: Rho GTPase activating protein 12; HCC: Hepatocellular carcinoma; TKI: Tyrosine kinase inhibitor.

Figure 2 Single-cell RNA sequencing data analysis of 18 primary hepatocellular carcinoma and non-hepatocellular carcinoma tissue samples in GSE149614. A: Cell distribution of hepatocellular carcinoma and non-hepatocellular carcinoma groups in the samples; B: Distribution of included samples. Different colors represent different tissue samples; C: Main cell types; D: Rho GTPase activating protein 12 expression distribution. ARHGAP12: Rho GTPase activating protein 12; HCC: Hepatocellular carcinoma; UMAP: Uniform manifold approximation and projection.

Figure 3 Expression levels of Rho GTPase activating protein 12 in various cell types in the TISCH2 database. ARHGAP12: Rho GTPase activating protein 12.

Figure 4 Investigation of the potential mechanisms of Rho GTPase activating protein 12 in the focal adhesion pathway. A: Enrichment analysis; B: Focal adhesion pathway scores in various cell types; C: Number of interactions in various cell types; D: Strength of interactions in various cell types. FA: Focal adhesion.

Figure 5 Analysis of the MK communication network. A: Heatmap of outgoing and incoming signal patterns; B: Ligand-receptor network of MK signaling; C: Heatmap plot of MDK-(integrin alpha 6 + integrin β-1) expression. ITGA6: Integrin alpha 6; ITGB1: Integrin β-1; FA: Focal adhesion.

Figure 6 Integrated analysis on Rho GTPase activating protein 12 expression in hepatocellular carcinoma. A: Forest plot; B: Summary receiver operating characteristic curve; C: Egger’s; D: Begg’s. SMD: Standardized mean difference; CI: Confidence interval; sROC: Summary receiver operating characteristic; AUC: Area under the receiver operating characteristic curve.

Figure 7 Expression of Rho GTPase activating protein 12 protein in hepatocellular carcinoma tissues. A: Immunohistochemistry staining of control and hepatocellular carcinoma samples; B: Violin plots and receiver operating characteristic curves; C: Comprehensive expression levels of Rho GTPase activating protein 12 protein. ARHGAP12: Rho GTPase activating protein 12; HCC: Hepatocellular carcinoma; SMD: Standardized mean difference; CI: Confidence interval; AUC: Area under the receiver operating characteristic curve.

Figure 8 Relationship of Rho GTPase activating protein 12 with clinical pathological parameters in hepatocellular carcinoma. A: Comprehensive prognostic levels of Rho GTPase activating protein 12; B: Vascular invasion; C: T stage; D: N stage. ARHGAP12: Rho GTPase activating protein 12; CI: Confidence interval; OS: Overall survival; HR: Hazard ratio.

Figure 9 High expression of Rho GTPase activating protein 12 under tyrosine kinase inhibitors treatment. A: Forest plot showing elevated expression of Rho GTPase activating protein 12; B: Summary receiver operating characteristic curve plot. SMD: Standardized mean difference; CI: Confidence interval; sROC: Summary receiver operating characteristic; AUC: Area under the receiver operating characteristic curve.

Figure 10  Potential regulatory mechanisms of Rho GTPase activating protein 12. A: Intersection of tyrosine kinase inhibitor-resistant genes, upregulated differentially expressed genes from bulk high-throughput data, and Rho GTPase activating protein 12 positively correlated genes; B: Enrichment analysis; C: Intersection of genes in the focal adhesion pathway from single-cell RNA sequencing and bulk RNA data. TKI: Tyrosine kinase inhibitor.

Figure 11  Sensitivity analysis of Rho GTPase activating protein 12 to tyrosine kinase inhibitors and immunotherapy. A: Relationship between Rho GTPase activating protein 12 expression and immune escape, immunotherapy; B: Relationship between Rho GTPase activating protein 12 expression and the intensity of tyrosine kinase inhibitors treatment. ARHGAP12: Rho GTPase activating protein 12.