High p53 Protein Level Is a Negative Prognostic Marker for Pancreatic Adenocarcinoma

Int J Mol Sci. 2024 Nov 16;25(22):12307. doi: 10.3390/ijms252212307.

Abstract

Pancreatic adenocarcinoma is one of the most aggressive types of cancer. Among different mechanisms generally believed to be important for the development of cancer, aberrant regulation of the p53 protein is a well-known and common feature for many cancer entities. Our work aims to analyze the impact of p53 deregulation and proteins encoded by p53 target genes on the survival of patients suffering from pancreatic adenocarcinoma. We, therefore, focused on the analysis of the selected collective for the TP53 mutation status, the p53 protein level, their correlation, and possible impacts on the prognosis/survival. We compared and analyzed a set of 123 patients. We have extracted information regarding the TP53 mutation status, p53 protein levels, the level of proteins encoded by prominent p53 target genes, and information on the overall survival. Survival analyses were displayed by Kaplan-Meier plots, using the log-rank test, in order to check for statistical significance. Protein levels were compared using the Mann-Whitney Test. We did not find any statistically significant correlation between the TP53 mutation status and the survival of the patients. Moreover, we have not found any significant correlation between the protein amount of prominent p53 target genes and the patients' survival. However, we see a significant correlation between the p53 protein level in cancer samples and the overall survival of pancreatic adenocarcinoma patients: patients having tumors with a p53 protein level within the upper quartile of all measured cases show a significantly reduced survival compared to the rest of the patients. Thus, in pancreatic adenocarcinoma, the p53 protein level is a relevant marker for prognosis, and cancers having a high p53 protein amount show a shortened patients' survival. In contrast, for this cancer entity, the TP53 mutation status or the protein amount of prominent p53 target genes on their own seems not to have a significant impact on survival.

Keywords: p53; pancreatic adenocarcinoma; patient survival.

MeSH terms

  • Adenocarcinoma* / genetics
  • Adenocarcinoma* / metabolism
  • Adenocarcinoma* / mortality
  • Adenocarcinoma* / pathology
  • Aged
  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mutation*
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / metabolism
  • Pancreatic Neoplasms* / mortality
  • Pancreatic Neoplasms* / pathology
  • Prognosis
  • Tumor Suppressor Protein p53* / genetics
  • Tumor Suppressor Protein p53* / metabolism

Substances

  • Tumor Suppressor Protein p53
  • Biomarkers, Tumor
  • TP53 protein, human

Grants and funding

We acknowledge support from the Open Access Publication Fund of the University of Tübingen.