G Protein-Coupled Receptor Kinase 4 Is a Novel Prognostic Factor in Hepatocellular Carcinoma.

Purpose: We previously reported that G protein-coupled receptor kinase (GRK) 4 halts cell cycle progression and induces cellular senescence in HEK293 cells. The present study was aimed at assessing the prognostic value of GRK4 in hepatocellular carcinoma (HCC). Methods: GRK4 expression was detected by immunohistochemistry in paired tumoral and peritumoral tissues of 325 HCC patients. One hundred and twenty-six patients from Western China were utilized as a training cohort to develop a nomogram, while 86 patients from Eastern China were used as a validation cohort. The proliferation and migration of lentiviral-GRK4 expressing HepG2 cells were determined by MTT and wound healing assays. Results: GRK4 was differentially expressed in HCC tissues. Tumoral GRK4 intensity, tumor type, and T stage were independent prognostic factors and used to form a nomogram for predicting overall survival (OS), which obtained a good concordance index of 0.82 and 0.77 in training and validation cohort, respectively. The positive and negative prediction values with nomogram were, respectively, 83% and 75% in training cohort and 100% and 52% in validation cohort. Patients with nomogram scores > 32 and 78 showed high risk for OS. Proliferation and motility capabilities were significantly restrained in GRK4-overexpressing HCC cells.