Overexpression of GRK6 associates with the progression and prognosis of colorectal carcinoma.

Abstract

There are a limited number of studies reporting on the expression of G protein-coupled receptor kinase 6 (GRK6) in colorectal carcinoma (CRC). The aim of the present study was to investigate and examine the clinical value of GRK6 expression in human CRC. The expression of the GRK6 protein was determined in CRC tissues (n=83) and in normal colorectal tissues (n=19) by immunohistochemical (IHC) analysis. In addition, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was conducted to investigate GRK6 mRNA levels in matched pairs of cancerous and non-cancerous fresh frozen tissues from 19 patients with CRC. Furthermore, GRK6 protein levels were evaluated in matched pairs of cancerous and non-cancerous fresh frozen tissues from 19 other patients with CRC by western blot analysis. The expression of GRK6 was significantly upregulated in patients with CRC as indicated by IHC analysis (P=0.028). The results of RT-qPCR and western blotting confirmed that GRK6 mRNA and protein levels were upregulated in CRC tissues compared with matched adjacent non-cancerous tissues (P<0.05). Additionally, GRK6 protein expression was significantly associated with histological differentiation (P=0.001), lymph node invasion (P=0.45), venous invasion (P=0.009), depth of invasion (P=0.026), distant metastasis (P<0.0001) and TNM stages (P=0.020). Survival analysis using the Kaplan-Meier method indicated that patients with high GRK6 expression levels exhibited lower overall survival rates compared with patients with low GRK6 expression. Multivariate analysis using the Cox proportional hazards model indicated that the expression levels of GRK6 (P=0.003) were independent prognostic factors for overall survival in patients. The overexpression of GRK6 in patients with CRC may serve as an independent predictor of patient outcome.