Cyclin D1 overexpression correlates with poor tumor differentiation and prognosis in gastric cancer.

Overexpression of cyclin D is associated with the molecular tumorigenesis of gastric cancer. The purpose of the present study was to investigate the expression of cyclin D in human gastric cancer and to determine the potential correlations between cyclin D expression and clinicopathological characteristics of specific histological types, as well as its prognostic significance. In the present study, the expression of the cyclin D1 (), cyclin D2 () and cyclin D3 () genes in gastric cancer patients was explored using the Oncomine database, and their correlation with overall survival (OS) and progression-free survival (PFS) was evaluated using Kaplan-Meier analysis. The prognostic significance of CCND1 protein expression was evaluated by western blot analysis of 32 matched specimens of gastric adenocarcinomas and normal tissues obtained from patients treated at the National Cheng Kung University Hospital (Tainan, Taiwan). Analysis of the Oncomine cancer microarray database revealed that gene expression was significantly increased in gastric intestinal-type adenocarcinoma, while was significantly increased in diffuse gastric adenocarcinoma, gastric intestinal-type adenocarcinoma and gastric mixed adenocarcinoma. Kaplan-Meier analysis indicated that overexpression of was associated with reduced OS and PFS. In addition, overexpression of and downregulation of were significantly correlated with receptor tyrosine-protein kinase erb-2-negative tumors and poor differentiation. The ratio of relative expression (expressed as the /β-actin ratio) in tumor tissues compared with that in normal tissues was correlated with poor differentiation (P=0.0018). In summary, overexpression is associated with shorter survival in patients with gastric cancer and with poorly differentiated tumors.