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. 2022 Sep 2;13:955133. doi: 10.3389/fgene.2022.955133

FIGURE 4.

FIGURE 4

Protein kinases are involved in the development of NEPC. (A) PCA plot separated the PC tissues using expression data clustered into CRPC and NEPC (SCC of prostate). The blue, brown, and plots represent NEPC (SCC of prostate) and CRPC, respectively. (B) Hierarchical clustering of protein kinase differential expression profifiles among the CRPC group and NEPC (SCC of prostate) group in 49 samples. The heat maps are based on expression values of signifificantly differentially expressed protein kinases (p < 0.05) detected by microarray probes. ‘‘Red’’ and ‘‘Blue’’ indicate expression above and below, respectively, relative expression. (C) Biological process enrichment of the protein kinases. In biological process enrichment, protein kinases were primarily associated with the phosphatidylinositol metabolic process, signal transduction, the protein modification process, and protein phosphorylation. (D) KEGG pathway enrichment analyses demonstrate the signifificance of protein kinases. Protein kinases were mainly associated with several signaling pathways that could affect PC progression in the analysis of KEGG (p < 0.01). (E) Selected protein kinases with increasing expression, which were associated with phosphorylated kinase substrate and targeted drugs as indicated by Venn diagrams: four protein kinases were selected. (F) The heat map shows the increasing expression during NEPC transdifferentiation of the 27 selected phosphorylated and drug-targeted protein kinases. ‘‘Red’’ and ‘‘Blue’’ indicate expression above and below, respectively, relative expression. The heat maps are based on expression values of signifificantly differentially expressed protein kinases (p < 0.05) detected by microarray probes. (G) Immunohistochemical staining of the CRPC patient’s prostate tissue and the NEPC patient’s prostate tissue, including PSA, p-CHEK1, p-KIT, p-BUB1 and p-PAK2 indicators. NEPC, neuroendocrine prostate cancer; CRPC, castration-resistant prostate cancer; KEGG, Kyoto Encyclopedia of Genes and Genomes pathway; PCA, principle component analysis; PC, prostate cancer; SCC, small cell carcinoma.