Sami Baccouche*, Ahmed Rebai, Mounir Frikha, Jamel Daoud, Rachid Jlidi and Ali Gargouri
Background: The presence of a functional p53 protein is a key factor for the appropriate suppression of cancer development. The tumor suppressor p53 accumulates under stressful conditions, such as DNA damage, heat shock, hypoxia and/or proto-oncogene activation, although conflicting reports exist on its transcriptional activity. A loss of p53 activity, by mutations or inhibition, is often associated with human malignancies. This work investigated the significant value of p53 accumulated in IDBC (Invasive Ductal Breast Carcinoma) and at the same time tries to arise different supports of this value.
Results: To ensure this objective, we referred to two types of statistical analysis, the chi-square and logistic regression analysis. They confirmed the poor prognosis of p53 accumulated in IDBC (β*=-0.456 with p=0.00001) and showed that the independent variables (MDM2, BCL2, BAX and ER) formed an interesting model to explain the significant value of p53 accumulated in the IDBC. The predictive value of the model including the four biomarkers is AUC=93.5%, showing that if we take the expression status of the four biomarkers, we can deduce the status of p53 with a reliability of 93.5%.
The residual term, representing 6.5% and involved in this significant value, corresponds to intrinsic modifications of p53: Alterations of the TP53 gene, p53-oncoprotein interaction or cytoplasmic sequestration. In fact, following the IHC results of three different antibodies that recognize wild type or mutant p53, we examined the status of polymorphism 72, which may inform LOH (loss of heterozygozity). We found LOH associated with TP53 mutations in the context of down-regulated p53 target genes revealed by IHC. Although wild type in some cases, p53 loses its transcriptional activity; this may be due to oxidation of cysteine residues in the core domain, either iSAPP interaction or its cytoplasmic sequestration.
Conclusion: p53 accumulated in IDBC had a significant value and the etiological factors of this value should be target for effective therapy.
Published Date: 2024-05-17; Received Date: 2024-04-02
