p53 Antibodies as a Diagnostic Marker for Cancer: A Meta-Analysis

Abstract

Importance: The protein p53 is an unequivocal tumor suppressor that is altered in half of all cancers. The immune system produces systemic p53 autoantibodies (p53 Abs) in many cancer patients. Objective: This systemic review and meta-analysis focuses on the prognostic value of p53 Abs expressed in the serum of patients with solid tumors. Data Sources: All the clinical investigations were searched on PubMed from the first study dated 1993 until May 2021 (date of submission of the manuscript). Study Selection: Studies were included that met the following criteria: 1) participants with cancer; 2) outcome results expressed in relation to the presence of a p53 antibody; 3) a primary outcome (disease-free survival, overall survival or progression-free survival) expressed as hazard ratio (HR). The following exclusion criteria were used: 1) insufficient data available to evaluate outcomes; 2) animal studies; 3) studies with less than 10 participants. As a result, 12 studies were included in the analysis. Data Extraction and Synthesis: PRISMA guidelines were used for abstracting and assessing data quality and validity by three independent observers. The summary estimates were generated using a fixed-effect model (Mantel–Haenszel method) or a random-effect model (DerSimonian–Laird method), depending on the absence or presence of heterogeneity (I2). Main Outcome(s) and Measure(s): The primary study outcome was to determine the prognostic value of p53 Abs from a large population of patients with solid tumors, as determined before data collection. Results: In total, 12 clinical studies involving 2094 patients were included in the meta-analysis, and it was determined that p53 Abs expression in the serum significantly correlated with poorer survival outcomes of cancer patients (95% CI 1.48 [1.24, 1.77]; p < 0.00001). Conclusions and Relevance: This is the first meta-analysis proving the diagnostic utility of p53-Abs for cancer patients in predicting poorer outcomes. The serum-p53 value (s-p53-value) may be useful for future theranostics.

A Luminex Approach to Develop an Anti-Tumor-Associated Antigen Autoantibody Panel for the Detection of Prostate Cancer in Racially/Ethnically Diverse Populations

“…High frequencies of positive autoantibody reactions and high AUC (AUC > 0.860) were observed for autoantibodies to p53 and HSP60, suggesting their potential as diagnostic biomarkers for PCa. Anti-p53 autoantibody has been demonstrated to be associated with various types of cancer including PCa [ 15 , 28 , 29 ]. Consistent with this, the Luminex assay detected an anti-p53 response in 51.6% (47/91) of PCa patients.…”

Bioinformatics Analysis Reveals the Related Role of miR-511-5p in the Progression of Breast Cancer

“…Moreover, CCND1, CCNE1, and CHEK1 were related with P53 pathways, and CCND1, CCNE1, COL5A2, FN1, and BRCA1 were related with PI3K/AKT pathways. P53 serves as a tumor inhibitor which is inactivated or mutant in many cancer cells [ 21 ]. For breast cancer, P53 mutant has also been reported as a biomarker event, and decreased P53 has a direct connection with the poor outcomes of the sufferers [ 22 ].…”

Unraveling the complex interplay between anti-tumor immune response and autoimmunity mediated by B cells and autoantibodies in the era of anti-checkpoint monoclonal antibody therapies

“…Nevertheless, it should be mentioned that, autoreactive antibodies are not always associated with anti-tumor effector function but can be pro-tumoral. In fact, certain antigenic specificities of serum antibodies have been correlated with poor prognosis, such as p53 ( 27 ).…”