Abstract
Polo-like kinase 4 (PLK4), belonging to serine/threonine kinase family, is critical for centriole replication and cell cycle progression. PLK4 has been proposed as a tumor suppressor in hepatocellular carcinoma (HCC). However, its expression and significance in HCC have not been well studied. In the present study, we found that PLK4 was markedly downregulated in both HCC cell lines and fresh cancer tissues, using quantitative real-time-PCR and western blot. Immunohistochemistry data also revealed that decreased expression of PLK4 was present in 72.4% (178/246) of HCC tissues, compared with the corresponding adjacent nontumorous tissues. Furthermore, PLK4 expression significantly correlated with clinicopathological parameters, including clinical stage (P = 0.034), serum α-fetoprotein (AFP) (P = 0.019) and tumor size (P = 0.032). Moreover, HCC patients with low PLK4 expression survived shorter than those with high PLK4 expression, as indicated by overall survival (P = 0.002) and disease-free survival (P = 0.012) assessed by the Kaplan–Meier method. In addition, multivariate analysis suggested PLK4 as an independent predictor of overall survival (HR, 0.556; 95%CI, 0.376−0.822; P = 0.003) and disease-free survival (HR, 0.547; 95%CI, 0.382−0.783; P = 0.001). Collectively, our study demonstrated that PLK4 was remarkably downregulated in HCC and could be served as a potential prognostic marker for patients with this deadly disease.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer, thirdly leading cancer-related death worldwide [1]
The Expression of Polo-like kinase 4 (PLK4) in HCC Cell Lines To examine the expression of PLK4 in HCC, we firstly detected its mRNA level in immortalized liver cell lines and HCC cell lines
We examined PLK4 expression in 20 paired HCC and the corresponding adjacent nontumor tissues, using qRT-PCR and western blot
Summary
Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer, thirdly leading cancer-related death worldwide [1]. The mortality rate of HCC has been increasing in China since the 1990 s, and HCC has became the second leading cause of cancer death [2]. Many risk factors, such as hepatitis B or C viral infection, alcohol consumption, aatoxinB1, and genetic predisposition have been identified as causes of HCC [3,4,5,6]. The pathogenic mechanism and inadequacy of early detection of HCC have not been clearly clarified. A large series of investigations are focused on the discovery of biological markers useful for HCC diagnosis and prognostic prediction to provide scientific guidance to clinical management
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