Prognostic value of decreased GRK6 expression in lung adenocarcinoma.

Abstract

In recent years, G protein-coupled receptor kinases (GRKs) have been implicated in cancer metastasis through phosphorylation of the activated form of G protein-coupled receptors. However, little is known of GRK6 expression in lung adenocarcinoma (LADC) and its potential prognostic value in LADC. In this study, protein expression of GRK6 was determined in LADC tissues (n=122) and normal lung tissues (n=45) by immunohistochemistry (IHC) analysis on tissue microarray (TMA). In addition, mRNA level of GRK6 in matched pairs of cancerous and non-cancerous fresh frozen tissues from 20 LADC patients was investigated using real-time quantitative PCR (qPCR). Furthermore, protein expression level of GRK6 was evaluated in matched pairs of cancerous and non-cancerous fresh frozen tissues from another 18 LADC patients. Univariate and multivariate analyses based on Cox proportional hazards regression models were performed to investigate the correlation between GRK6 expression and overall survival of LADC patients. According to the IHC analysis on TMA, GRK6 expression was significantly down-regulated in LADC patients, but high in normal lung tissue (P<0.001). Besides, our qPCR and western blot results confirmed GRK6 down-regulation in both mRNA and protein levels in LADC tissues as compared to matched adjacent non-cancerous tissues (all P<0.001). Additionally, For TMA slides, protein expression of GRK6 was significantly associated with staging (P=0.030), pathology grade (P=0.036). Consistent with the associated poor clinicopathologic features, patients with GRK6 low expression tumors had a worse overall survival compared to patients with GRK6 high expression tumors. Further multivariate analysis using the Cox proportional hazards model revealed that GRK6 expression level (P=0.004) was an independent prognostic factor for overall survival. These findings indicate for the first time that decreased expression of GRK6 may serve as an independent predictor of overall survival in LADC patients.