Correlation between expression of p53, p21/WAF1, and MDM2 proteins and their prognostic significance in primary hepatocellular carcinoma

Abstract

BackgroundTumor Protein p53 (p53), cyclin-dependent kinase inhibitor 1A (p21/WAF1), and murine double minute 2 (MDM2) participate in the regulation of cell growth. Altered expression of these gene products has been found in malignant tumors and has been associated with poor prognosis. Our aim was to investigate the expression of the 3 proteins in hepatocellular carcinoma (HCC) and their prognostic significance.MethodsWe examined p53, p21/WAF1, and MDM2 expression in 181 pairs of HCC tissues and the adjacent hepatic tissues by performing immunohistochemistry and examined the expression of the 3 proteins in 7 pairs of HCC tissues and the adjacent hepatic tissues by using western blot analysis.ResultsThe expression of p53, p21/WAF1, and MDM2 in the HCC tissues was significantly higher than those in the adjacent hepatic tissues (P < 0.05). A statistical correlation was observed between p53 and p21/WAF1 expression in HCC tissues (R = 0.195, P = 0.008). A statistical correlation was observed between expression of p53 and p21/WAF1 (R = 0.380, P = 0.000), p53 and MDM2 (R = 0.299, P = 0.000), p21/WAF1 and MDM2 (R = 0.285, P = 0.000) in 181 liver tissues adjacent to the tumor. Patients with a low pathologic grade HCC (I+II) had a higher tendency to express p53 on tumor cells than the patients with high pathologic grade HCC (III+IV) (P = 0.007). Survival analysis showed that positive p21/WAF1 expression or/and negative MDM2 expression in HCC was a predictor of better survival of patients after tumor resection (P < 0.05).ConclusionsThe proteins p53, p21/WAF1, and MDM2 were overexpressed in all the HCC cases in this study, and p53 and p21/WAF1 overexpression were positively correlated. The expression of p21/WAF1 and MDM2 can be considered as 2 useful indicators for predicting the prognosis of HCC.

Effects of harmaline on cell growth of human liver cancer through the p53/p21 and Fas/FasL signaling pathways

“…Following DNA damage and p53 activation, transcription of p21 is induced, which arrests cells in G 1 (21). In addition, p21 may act synergistically with proliferating cell nuclear antigen to inhibit DNA synthesis (22).…”

MiR-663, a microRNA targeting p21WAF1/CIP1, promotes the proliferation and tumorigenesis of nasopharyngeal carcinoma

“…Immunohistochemistry Immunohistochemistry was performed as described previously (Yun et al, 2007;Zhang et al, 2009). Briefly, after blocking, the sections were incubated with primary antibodies overnight (antip21 (Cell Signaling Technology), 1:25; anti-Ki67 (Santa Cruz Biotechnology), 1:1), followed by incubation with secondary antibodies, and further incubation with the Streptavidin-Biotin complex (Dakopatts, Glostrup, Denmark).…”

Association Between MDM2 Promoter SNP309 T/G Polymorphism and Liver Cancer Risk - a Meta-analysis

“…Thus, there is obvious biochemical evidence supporting the association between MDM2 SNP309 T/G polymorphism and liver cancer risk. Besides, MDM2 overexpression is also associated with poor survival and is a useful predictive factor for poor prognosis in patients with liver cancer (Zhang et al, 2009), which further identified the role of MDM2 in liver carcinogenesis and progression.…”