Expression of Cyclin E, proliferation cell nuclear antigen and matrix metalloproteinase-9 in colorectal carcinoma cells and the significance

Abstract

Objective To explore the effect of the expression of cell cycle regulators on the development and prognosis of colorectal carcinoma. Methods The surgicall resected tissues from 128 cases of colorectal cancer were collected in our hospital from June 2012-December 2015 December. The expression levels of Cyclin E, proliferation cell nuclear antigen (Ki-67) and matrix metalloproteinase (MMP)-9 were detected by immunohistochemieal staining in the large intestine mucosa from 128 cases of carcinoma and 24 samples of normal mucosa.χ2 test, single factor analysis of variance, Kaplan-Meier survival rate curve analysis and Log-rank test were applied.P<0.05 was considered to be statistically significant difference. Results The positive rate of Cyclin E, Ki-67 and MMP-9 was significalntly higher in colorectal carcinoma than in normal mucosa (χ2=5.203, P=0.013). The expression of Cyclin E in Duke’s stage A was markedly higher than in Duke’s stages B, C and D (χ2=10.331, P=0.001), and it was higher in cases with negative lymph node metastasis than in those with positive lymph node metastasis (χ2=6.732, P=0.005). The expression of Cyclin E was not correlated with the prognosis of the cases with lymph node metastasis. The down-regulated expression or deficiency of MMP-9 was related to advanced Duke’s stages (χ2=7.201, P=0.003) and lymph node metastasis (χ2=12.072, P=0.000). The Ki-67 expression was not associated with the carcinoma localization, advanced Duke’s stages and prognosis. There were 44 deaths from 128 patients, accounting for 39.29%, with 24, 14 and 36 cases positive for, and 20, 30 and 8 cases negative for Cyclin E, Ki-67 and MMP-9 expression, respectively. The 5-year survival rate in Cyclin E positive and negative expression groups was 63.64% and 56.52% respectively, with no significant difference (χ2=0.958, P=0.273). The 5-year survival rate in MMP-9 positive expression group was 73.33%, significantly higher than that in MMP-9 negative group (46.15%, χ2=3.143, P=0.035). The 5-year surfival rate in Ki-67 positive group (61.70%) and negative group (55.56%) showed no significant difference (χ2=0.827, P=0.419). The expression of Cyclin E was positively correlated with Ki-67 (r=0.391, P=0.019), MMP-9 and Ki-67 showed no significant correlation (r= -0.109, P=0.387), and MMP-9 and Cyclin E expression had no significant correlation (r=-0.168, P=0.183). Conclusion The overexpression of Cyclin E and decline or deficiency of MMP-9 expression might accelerate the progression of the cell cycle and promote the carcinogenesis of colorectal carcinoma. The overexpression of Cyclin E might be a relatively early event in initiation of colorectal carcinoma. The decline or deficiency of MMP-9 expression might promote the development and metastasis of colorectal carcinoma, and it could be an indicator for unfavorable prognosis. Key words: Colorectal carcinoma; Cyclin E; Matrix metalloproteinase-9; Cell cycle; Prognosis