1. Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
2. Department of Pathology, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
3. Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan.
4. National Tainan Second Senior High School, Tainan, Taiwan.
5. Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.
6. Department of Cosmeceutics, China Medical University, Taichung, Taiwan.
7. Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
8. Chinese Medicine Research Center, China Medical University, Taichung, Taiwan.
9. Department of Internal Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
10. Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
11. Department of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
12. Department of Food Science and Technology, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
Background: Globally, gastric cancer is ranked 4th and 3rd in terms of incidence and mortality rate among all cancer types. This study aimed to examine the relationship between G protein-coupled receptor kinase 3 (GRK3) and gastric cancer prognosis and investigate the role of GRK3 in gastric cancer carcinogenesis.
Methods: GRK3 level in gastric tissues and cells were determined using immunohistochemistry and immunoblotting. Kaplan-Meier analysis with the log-rank test was employed to evaluate the relationship between GRK3 expression and gastric cancer prognosis. RNAi technology was applied to examine the effects of GRK3 inhibition on gastric cancer proliferation and spread.
Results: GRK3 overexpression was correlated significantly with lymphatic metastasis (P = 0.0011), distant metastasis (P < 0.0001), TNM stage (P = 0.0035), and vascular invasion (P = 0.0025). Kaplan-Meier survival analysis showed that the disease-free survival and overall survival of patients with high GRK3 expression were significantly shorter than those of patients with low GRK3 expression. Multivariate Cox regression analysis also showed that the overexpression of GRK3 was an independent prognostic biomarker of gastric cancer (P = 0.029). In cultured gastric cancer cells, GRK3 knockdown inhibited cell proliferation, migration, and invasion. Further analysis revealed that more GRK3-knockdown cells were in G0/G1 phase and few cells were in S phase, thereby inhibiting cell proliferation.
Conclusions: GRK3 overexpression can be a candidate biomarker for gastric cancer prognosis. GRK3 is also a potential therapeutic target for gastric cancer.
Keywords: GRK3, Gastric cancer, Prognosis, Biomarker