G protein-coupled receptor kinase 4 as a prognostic factor for hepatocellular carcinoma

Abstract BACKGROUND: GRK4 has been the least understood member of the GRKs and its role in cancer has been rarely investigated. We recently reported that GRK4 halts cell cycle progression and induces cellular senescence in HEK293 cells, which involoves in pathways of cellular development, proliferation, and cell death. The present study aimed at assessing the prognostic value of GRK4 in hepatocellular carcinoma (HCC). METHODS: Expression of GRK4 was detected by immunohistochemistry in paired tumor and peritumoral tissues. In total, 126 patients with HCC from Western China were utilized as the training cohort to develop the nomogram. Eighty-nine cases from Eastern China were used to validate the model’s performance. RESULTS: GRK4 was expressed at lower levels in tumors than in peritumoral tissues in both training (p<0.001) and validation cohorts (p<0.001). Tumoral GRK4 intensity score, tumor type and T stage were independent prognostic factors and used to form a nomogram for predicting overall survival, which obtained a good concordance index of 0.82 and 0.77 in training and validation cohort, respectively. In the training cohort, the positive and negative prediction values with the nomogram were 83% and 75%, respectively, and in the validation cohort was 100% and 52%, respectively. Patients with nomogram scores greater than 32 and 78 were considered to have a high risk for OS. CONCLUSIONS: Low GRK4 expression in tumor tissues indicates poor clinical outcomes. The nomogram including tumoral GRK4 expression would improve the predictive accuracy of OS in HCC patients.