Phosphorylation of p53 Serine 15 Is a Predictor of Survival for Patients with Hepatocellular Carcinoma

Abstract

Background. Hepatocellular carcinoma (HCC) is one of the most common malignant cancers with a poor prognosis. Several commonly investigated immunohistochemical markers in resected HCC have potential prognostic value, but the prognostic utility of p53 expression in HCC has remained elusive. Aim. To evaluate the prognostic value of p53 and p53 phosphorylation at serine 15 (p53 Ser15-P) in patients with HCC. Methods. Surgically resected tumors from 199 HCC patients were analyzed for p21, p53, p53 Ser15-P, and proliferating cell nuclear antigen (PCNA) expression using immunohistochemistry. Results. Stratifying by the expression of p53 Ser15-P (P = 0.016), but not by p53 (P = 0.301), revealed significantly different survival outcomes in patients with HCC. Moreover, our analysis demonstrated that patients who were PCNA-positive and p53 Ser15-P–negative had significantly worse survival outcomes (P = 0.001) than patients who were PCNA-positive and p53 Ser15-P–positive. Conclusions. P53 Ser15-P is associated with poor outcomes in patients with HCC, and this prognostic marker is useful for predicting the survival of patients with PCNA-positive HCC.

Dysregulated Phosphorylation of p53, Autophagy and Stemness Attributes the Mutant p53 Harboring Colon Cancer Cells Impaired Sensitivity to Oxaliplatin

“…Phosphorylation, a key posttranslational modification is known for its potent role in rendering wild-type p53 protein’s functionality as a tumor suppressor ( 27 ). In particular, the stabilization and activation of p53 in response to genotoxic stress induced by platinum-based therapeutics are reported to be facilitated via phosphorylation of the serine residues ( 28 , 29 ). Based on these reports, we intended to determine the phosphorylation of N-terminal and C-terminal serine residues of p53 protein in wild-type p53 bearing HCT 116 and mutant p53 bearing HT 29 colon cancer cells in response to OX treatment.…”

Liver Lipids of Patients with Hepatitis B and C and Associated Hepatocellular Carcinoma

“…It is likely that p53 activity is controlled by multiple modifications and not by phosphorylation of a single-site [ 28 ]. High p53S15 expression in HCC tissues of mostly HBV infected patients was related to longer survival [ 59 ]. Such an association did not exist for p53S392 [ 59 ].…”

“…High p53S15 expression in HCC tissues of mostly HBV infected patients was related to longer survival [ 59 ]. Such an association did not exist for p53S392 [ 59 ]. Correlations between p53S15 and clinicopathologial factors such as vascular invasion were not identified in that study.…”

“…Correlations between p53S15 and clinicopathologial factors such as vascular invasion were not identified in that study. Of note, p53S392 was positively associated with intrahepatic invasion [ 59 ]. Both of these isoforms positively correlated with p53 protein levels in the HCC tissues [ 59 ].…”

“…Of note, p53S392 was positively associated with intrahepatic invasion [ 59 ]. Both of these isoforms positively correlated with p53 protein levels in the HCC tissues [ 59 ]. In the HCC tissues studied herein, phosphorylated isoforms correlated with each other but none of these isoforms was associated with p53 protein levels.…”