Decreased expression of p39 is associated with a poor prognosis in human hepatocellular carcinoma

Abstract

The aims of this study are to investigate the relationship between p39 expression and clinicopathological parameters of hepatocellular carcinoma (HCC) and to evaluate the prognostic value of p39 for HCC patients. Real-time quantitative PCR and immunohistochemistry was used to measure p39 expression in tumor and adjacent nontumor samples. Relationships of p39 expression with clinical parameters and patient survival were analyzed. Real-time quantitative RT-PCR showed that the quantity of p39 mRNA in cancerous tissue was significantly lower than that in nontumor tissue (P < 0.001). Immunohistochemistry data confirmed that p39 protein was reduced in 64% of HCC. p39 expression was not influenced by chronic alcohol exposure or cirrhosis. Reduction in p39 was correlated with the HBV (P = 0.039), HCV (P = 0.011), and histological grade (P < 0.001). HCC patients with lower p39 expression had poorer overall survival rate than that with high expression (HR, 2.868; 95% CI, 1.451-5.670; P = 0.002). Together with other results, these results reveal that p39 expression was reduced in HCC tissue. p39 could be a useful clinical prognostic marker for hepatocellular carcinoma patients.

Clinical role and biological function of CDK5 in hepatocellular carcinoma: A study based on immunohistochemistry, RNA-seq andin vitroinvestigation

“…CDK5 and p35 were recently identified as a potent tumor suppressor in HCC. The decreased expression of p39 correlated with a poor overall survival rate [ 31 ]. Regulation of CDK5 activity promoted the proliferation of medullary thyroid carcinoma (MTC) [ 32 ].…”

The Emerging Role of Cdk5 in Cancer

“…In tissues from non-small cell lung cancer (NSCLC), breast, brain and nasopharyngeal cancer patients, increased Cdk5 and/or activator expression parallels advanced cancer stages, occurrence of lymph node metastasis, and overall poor 5-year survival, while low Cdk5 levels correlates with metastatic-free disease [14–19]. Somewhat remarkably abnormal low Cdk5 or activator tumor levels are also indicative of poor prognosis as in advanced gastric cancer [20] or hepatocellular carcinoma (HCC) [21]. More studies are needed to understand the molecular mechanisms by which Cdk5 and activators contribute to these cancers.…”

Cyclin-Dependent Kinase 5 (CDK5)-Mediated Phosphorylation of Upstream Stimulatory Factor 2 (USF2) Contributes to Carcinogenesis

“…Changes in the phosphorylation status are often accompanied with transcription factor regulation. Indeed, it has been shown that USF2 is a phosphoprotein [28,29] and that a number of tumor entities such as prostate cancer [30,31,32,33], hepatocellular carcinoma [34,35,36,37] and breast cancer [38,39,40] are associated with an aberrant USF2 function (for review see [13]). In addition, these cancers are also associated with high expression and activity levels of cyclin-dependent kinase-5 (CDK5) (for review see [41])).…”