Figure 1.
PTK7 was the most significantly deregulated kinase in metastatic HCC and was enriched in advanced HCC tumors. (A) A total of 509 commonly deregulated kinases in cancer were extracted from the nCounter Human Kinase Panel Gene List, and their expression pattern was examined in the TCGA-LIHC patient cohort. Thirty-five candidate kinases were overexpressed in tumor and advanced HCC, and ranked (from top to bottom) according to their extent of up-regulation and evaluated against the GSE45114 data set, which described transcriptomic profiles of nontumor and tumor tissues harvested from metastatic HCC samples and their nonmetastatic counterparts. The heatmap was constructed to represent the fold-change in the expression of each candidate kinase in HCC tumors compared with nontumor samples under a metastatic or nonmetastatic background. Only 3 kinases (TTK, PTK7, and CDC7, marked with an asterisk) were significantly overexpressed in metastatic HCC, and PTK7 was the most significantly deregulated. (B) Statistical evaluation of the fold change in PTK7 expression (tumor vs nontumor) for 228 pairs of HCC samples evenly grouped by their predicted risk of metastasis as described in the GSE14520 cohort by paired t test between each tumor/nontumor comparison. The predicted risk of metastasis was defined by the integral signature score of 161 metastatic genes that robustly correlated with recurrence and adverse clinical outcome.25 (C) The distribution of early and advanced HCC cases in the high-PTK7 and low-PTK7 samples of the TCGA-LIHC data set compared using the chi-squared test. (D) The overall survival distribution of patients with high or low PTK7 expression in the TCGA-LIHC data set compared using the Gehan–Breslow–Wilcoxon test. (E) Representative images of high-PTK7 staining from IHC on TMA containing tumor and nontumor samples of HCC patients. Scale bar: 100 μm. (F) The distribution of high- and low-PTK7 cases in tumor and nontumor samples of TMA compared using the chi-squared test. (G) The overall survival distribution of TMA patients with high or low PTK7 expression compared using the log-rank test. P values (∗P < .05, ∗∗P < .01, ∗∗∗P < .001).